bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipokines, Obesity, and Sex: Implications for the Central Control of Cardiovascular Function
Authors: Yosten Gina L. C.
Published: November 2023

In addition to the storage of lipids, adipose tissue contributes to energy homeostasis by producing multiple adipokines, such as leptin and nesfatin‐1, that regulate food intake and energy expenditure. Plasma levels of these adipokines, which inhibit appetite, increase as a function of adipocyte mass, thus decreasing food intake during times of energy excess. In addition to modulating energy intake, adipokines also impact cardiovascular function, particularly through activation of the sympathetic nervous system. Like leptin, nesfatin‐1 interacts with the central melanocortin system to exert its hypertensive effects. Interestingly, melanocortin neurons are heavily influenced by sex hormones, particularly estrogen, which regulates the responsiveness and activity of these neurons. The functional implication of this observation is that females may respond to the hypertensive effects of adipokines, like nesfatin‐1, differently than males. We previously reported that male rats exhibit significant, dose‐related increases in blood pressure following injection of nesfatin‐1 into the lateral cerebroventricle, and that this effect could be blocked by pretreatment with a melanocortin receptor antagonist. In contrast, the hypertensive effect of nesfatin‐1 in females appears to be dependent upon sex hormone levels, as the response to nesfatin‐1 was significantly attenuated in rats in proestrus and estrus (high estrogen). As with males, the hypertensive effect of nesfatin‐1 in females in diestrus (low estrogen) was blocked by pretreatment with the melanocortin receptor antagonist, SHU9119. However, a completely sexually dimorphic effect was observed with respect to nesfatin‐1's effect on angiotensin II‐stimulated drinking and blood pressure. Whereas nesfatin‐1 significantly inhibited angiotensin II‐induced water drinking in males, nesfatin‐1 enhanced angiotensin II's effects on water drinking and blood pressure in females. We propose that these sex‐related differences in the hypertensive effects of nesfatin‐1 are due to the modulatory activity of estrogen on nesfatin‐1‐responsive melanocortin neurons, and that loss of estrogen, as observed in menopause, will lead to enhanced nesfatin‐1 signaling and hypertension. Future studies investigating the ability of chronically administered nesfatin‐1 to promote hypertension using telemetric monitoring of blood pressure will be necessary to evaluate whether persistently high nesfatin‐1 levels alter cardiovascular function.

Support or Funding Information

National Institutes of Health, HL121456
Functional Innervation of Rat Mesenteric Arteries Is Regulated by Thyroid Hormones
Authors: Ferrer Mercedes , Ruiz Mireya , Alameda M. Teresa , Sagredo Ana , Fernández‐Lamo Iván , Guadaño Ana
Published: November 2023

Thyroid hormones (THs) have been shown to affect cardiovascular function, and we previously demonstrated the modulatory action of THs on the function of rat aorta through different endothelial factors. On the other hand, innervation regulates the function of mesenteric arteries, which contribute to the control of peripheral vascular resistance. In view of these data, the aim of this study was to investigate whether THs influence the function of adrenergic and nitrergic innervations. For this purpose, endothelium‐denuded mesenteric artery segments from control and thyroidectomized male Wistar rats (4 months‐old) were used to analyze: (i) the contractile response induced by electrical field stimulation (EFS); (ii) the effect of the alpha‐adrenergic receptor antagonist, phentolamine, or the nitric oxide (NO)‐synthase inhibitor, L‐NAME, on the EFS‐induced response; (iii) the vasomotor response induced by noradrenaline (NA) and by the NO donor, sodium nitroprusside (SNP); and (iv) the basal and EFS‐induced NO release. The results showed that hypothyroidism increased the EFS‐ and NA‐induced contraction, while it did not modify the reduced EFS‐induced response after phentolamine incubation. Regarding nitrergic innervation, hypothyroidism reduced the EFS‐induced NO release as well as its vasodilator action, and L‐NAME failed to modify the EFS‐induced contraction. These findings suggest a preventive role of THs on noradrenergic and nitrergic function of rat mesenteric artery.

Support or Funding Information

Supportedby grants (to M.F.) from the Fondo de Investigaciones Sanitarias (PI1100406), Comunidadde Madrid (S2013/ABI‐2783, “INSPIRA1‐CM”) and Fondo Europeo de DesarrolloRegional.
AT1 receptor blockade modifies MAPKs expression and attenuates myocardial remodeling in rats subjected to high‐fat diet‐induced obesity
Authors: Oliveira‐Junior Silvio Assis , Carvalho Marianna R , Ota Gabriel E , Morais Camila S , Pagan Luana U , Gomes Mariana J , Martinez Paula F , Fernandes Tiago , Oliveira Edilamar M , Okoshi Marina P , Okoshi Katashi , Campos Dijon H S , Cicogna Antonio C
Published: November 2023

Although mitogen‐activated protein kinases (MAPKs) are involved in cardiac remodeling in several experimental models, their role is controversial in obesity. This study analyzed MAPKs expression and cardiovascular parameters in rats with diet‐induced obesity treated with angiotensin II type 1 (AT1) receptor blocker.

Methods

Wistar rats (n=48) were fed a control (2.9kcal/g) or a high‐fat (3.6kcal/g) diet for 20 weeks. After, rats were assigned to four groups: control (C); obese (OB); control‐losartan (LC); and obese‐losartan (LOB). Losartan was administered in drinking water (30mg/kg/day) for four weeks. Angiotensin‐converting enzyme activity (ACE) was determined in serum. Cardiovascular evaluation included systolic blood pressure (SBP), echocardiogram, myocardial morphometric study, myosin heavy chain composition, and myocardial protein levels of extracellular signal‐regulated kinase (ERK1/2) and c‐Jun amino‐terminal kinase (JNK) quantification by Western blot.

Results

main results are presented in the Table.

Conclusion

The angiotensin II blocker losartan attenuates cardiac remodeling and modulates MAPKs expression in rats with high‐fat diet induced‐obesity.

Support or Funding Information

Financial support: CNPq; FUNDECT/MS

Variables
C
OB
LC
LOB

Body adiposity (%)
4.64±0.95
7.62±1.55*
5.14±1.24
7.87±1.69†

ACE (UF×103/min/mg)
447±124
578±171*
577±98*
584±35

SBP (mmHg)
108±15
104±21
88±11*
78±21#

Heart rate (beats/min)
255±28
258±38
256±22
273±36

LV relative thickness
0.317±0.024
0.308±0.021
0.322±0.024
0.320±0.023

LVESd (mm)
4.37±0.51
4.86±0.66*
4.28±0.61
4.54±0.042

Ejection Fraction (%)
0.856±0.039
0.830±0.052*
0.855±0.044
0.835±0.034

CSA (μm2)
115.6±15.2
125.6±29.1
115.5±23.2
114.8±18.2

CIF (%)
1.02±0.36
1.70±0.77*
1.03±0.59
1.23±0.61

β/α‐MyHC
1.05±0.20
1.44±0.61*
1.00±0.25
1.41±0.17†

Total ERK 1/2
1.00±0.09
1.45±0.27*
1.18±0.26
0.91±0.49#

p‐ERK 1/2
1.00±0.60
0.69±0,16
0.82±0.13
0.93±0,93

Total JNK
1.00±0.27
1.01±0.37
0.90±0.22
0.18±0.10#†

p‐JNK
1.00±0.32
0.88±0.28
0.92±0.17
0.22±0.11#†

Values expressed as mean and standard deviation; LV relative thickness: left ventricular (LV) systolic posterior wall thickness‐to‐LV end‐diastolic diameter ratio; LVESd: LV end‐systolic diameter; CSA: cardiomyocyte cross‐sectional area; CIF: collagen interstitial fraction; β/α‐MyHC: ratio between LV β‐ and α‐MyHC isoforms;

p<0.05 vs C;

p<0.05 vs OB;

p<0.05 vs LC;

ANOVA and Tukey's test.
Transcriptional landscape of the major adipose depots during early life reveals unique pathways during development
Authors: Fainberg Hernan , Alhaddad Ahmad , Alagal Reham , Birtwistle Mark , Davies Graeme , Castellanos Marcos , May Sean , Sacks Harold , Budge Helen , Symonds Michael
Published: November 2023

Introduction

The anatomical and final functional architecture of each adipose tissue within the body is mainly determined by the pronounced changes in transcriptional processes during early postnatal life. To date this has not been examined using a bioinformatics approach that would be predicted to provide novel insights on fat development. In sheep there is a rapid transition from brown to white adipose tissue over the first month of life coincident with the loss of uncoupling protein 1 and the rapid growth of each fat depot.

Methods

To gain insight into the developmental origins of the molecular changes within fat in early life we conducted a multi‐region transcriptome analysis from five major (epicardial, subcutaneous, perirenal, sternal and omental) adipose depots sampled at 7 and 28 days of age from young sheep (n=6 per group).

Results

By weighted gene co‐expression network analysis, we found that each developmental stage and fat depot can be segregated into a concise group with a small number of unique functional modules of co‐expressed genes. Each module exhibited temporal and spatial specificity and were associated with distinct biological processes. This indicates a consistent and a sequential order of transcriptional changes in each depot with age. These are indicative of different cellular origins, metabolism, environmental influence and functionality. In particular, we uncovered specific anatomical regional clusters of gene markers which were associated with distinctive cellular progenitor of brown adipocytes that were validated by cross‐age modular preservation. Furthermore, we observed an active repression in gene expression in sternal adipose tissue that appeared to be a depot‐autonomous effect. This could result in slower metabolism and potentially enable brown adipocyte trans‐differentiation.

Conclusions

Together, our results demonstrate that each adipose tissue depot follows an independent path of postnatal, which could be influenced by cell progenitor type as well as the immediate endocrine environment. Finally, we demonstrate that weighted gene co‐expression network analysis provides a valuable resource to dissect gene regulatory mechanisms.

Support or Funding Information

The Cardiometabolic Disease Research Foundation, Los Angeles, USA.
Brown Adipose Tissue Promotes Healthful Aging
Authors: Guers John J , Zhang Jie , Yoon Seonghun , Vatner Dorothy E , Vatne Stephen F
Published: November 2023

Brown adipose tissue (BAT) increases thermogenesis and metabolism and protects against the cold. The mouse model of Receptor for G Protein Signaling 14 (RGS14) knockout (KO) has increased BAT, as assessed by a greater BAT mass and brown adipocyte size than wild type littermates and lives 17% longer than wild type (WT) littermates, and is not only protected against the cold, but has improved glucose tolerance and exercise capacity. Thermogenic function was improved in RGS14 KO as reflected by a lower reduction, <0.05, in basal body temperature in response to a cold environment (4° C) in RGS14 KO (−3.0 ± 0.5%) than WT (−7.1 ± 0.4%). Twenty‐four hour oxygen consumption, measured by indirect calorimetry, was greater in RGS14 KO (87 ± 3.2 ml/kg/min), than WT mice (76 ± 3.2 ml/kg/min; p <0.05). Maximal treadmill exercise capacity, measured as distance, was greater in RGS14 KO mice (814 ± 64 m) than their WT littermates (597 ± 24 m; p<0.05). Glucose tolerance, as assessed by the area under the curve in a glucose tolerance test in response to glucose load, was also protected in RGS14 KO mice (7,376 ± 712) compared to their WT littermates (AUC: 10,907 ± 1208; p <0.05). The goal of this investigation was to determine if BAT could be the mechanism mediating these salutary effects. Accordingly, we transplanted BAT from RGS14 KO to their WT littermates. Thermogenic function was improved in BAT recipients (−5.2 ± 0.3 %) when compared to BAT donors (−7.4 ± 0.6 %; p<0.05). Oxygen consumption was greater in BAT recipients (71 ± 5 ml/kg/min) than donor mice (57 ± 4 ml/kg/min; p <0.05). BAT recipient mice ran a greater distance (569 ± 28 m) than BAT donors (424 ± 29 m; p <0.05). BAT recipients also had improved glucose tolerance with lower areas under the glucose curves (7,010 ± 1,193) than their BAT donors (11,013 ± 1685; p <0.05). Thus WT receiving the BAT transplant exhibit improved cold tolerance, glucose tolerance and exercise capacity, similar to what is observed in RGS14 KO with intact BAT, and the RGS14 KO BAT donors lose their protection and have a phenotype similar to WT. These findings suggest that BAT mediates a number of novel mechanisms important for healthful aging.

Support or Funding Information

This work is supported by NIH grant: R01HL124282
Modulation of Hepatic Mineral Concentrations in Bile Acid‐Induced Fatty Liver
Authors: HORI SHOTA , Tanaka Yasutake , Tsuneki Ikuya , Hanai Taketo , Hara Hiroshi , Shimizu Hidehisa , Ishizuka Satoshi
Published: November 2023

Background & Aims

Bile acids (BAs) promote lipid absorption as a detergent and a high fat diet consumption promotes its secretion. In our previous study, we found that a diet supplemented with cholic acid (CA), a major primary BA increasing during aging, induces non‐obese fatty liver in rats. The CA‐induced fatty liver seems represent some symptoms at an early stage of fatty liver. On the other hand, hepatic iron is associated with severity of fatty liver disease but little is known about the roles of iron in the early stage of fatty liver development. Thus, we investigated whether distribution of minerals in the body is involved in the CA‐induced fatty liver.

Methods

Rats were fed diets either with or without CA‐supplementation for 13 weeks. BAs were analyzed in portal vein, liver, and cecum with LC‐MS. Mineral concentrations (Fe, Ca, Mg, Mn, Zn, and Cu) in liver, aorta plasma, renal cortex, and feces were analyzed with ICP‐MS. Several parameters associated with fatty liver were analyzed.

Results

Cecal concentration of deoxycholic acid, the secondary BAs from CA, increased significantly in the CA‐fed rats. In the portal plasma, significant increases in CA and taurocholic acid (TCA) levels were observed in the CA‐fed rats. Prominent increases in the concentration of TCA and taurodeoxycholic acid as well as lipid accumulation were found in the liver of the CA‐fed rats. A significant decrease was observed in hepatic Fe in the CA‐fed rats, whereas there were significant increases of Ca, Mg, and Mn in the liver. Principal component analysis indicated hepatic iron concentration was closely associated with the lipid accumulation in the liver. No significant difference was observed in concentration of ferritin in aorta plasma between two groups although Fe concentration in aorta plasma decreased significantly in the CA‐fed rats, suggesting decrease in the amount of functional iron in the CA‐fed rats.

Conclusion

Iron deficiency is reported to cause a variety of changes in host energy metabolism such as increases of glucose uptake and lipogenesis as well as decreases of β‐oxidation in the liver. Therefore, the decrease of hepatic functional iron in the CA‐fed rats may be involved in the development of the lipid accumulation.
The Effect of Alcohol Consumption on Adipokine Secretion
Authors: DeGroat Ashley R. , Peterson Jonathan M.
Published: November 2023

The goal of this project was to establish the effect of alcohol consumption on adipose tissue‐derived secreted factors; adiponectin and C1q TNF Related Proteins 1–3 (CTRP1‐3). Alcoholic Fatty Liver Disease (AFLD) is caused by excessive alcohol consumption and is a leading cause of liver related mortalities, with currently no treatments available. Both adiponectin and CTRP3 have been shown to reduce excessive hepatic lipid accumulation, and CTRP1 and CTRP2 have both been linked to beneficial effects on lipid metabolism. Further, adiponectin has been shown to decrease with alcohol consumption. Therefore, we propose that excessive alcohol consumption will reduce circulating levels of not only adiponectin but other adipokines, specifically CTRP1‐3. The deregulation of adipokine secretion can contribute to the development of hepatic insulin resistance, inflammation, and steatosis. To test the effects of alcohol consumption on adipokines, 12‐week old female mice were fed a Lieber‐Decarli alcohol diet (5% ETOH by volume) for either 10‐days ending with a binge (chronic plus binge model) or for 6‐weeks with no binge added (chronic model). Serum was collected from the mice and CTRP1, CTRP2, CTRP3, and adiponectin levels were examined by immunoblot analysis.

RESULTS

In response to the chronic plus binge model adiponectin and CTRP1 levels decreased and no change in CTRP2 or CTRP3 levels were observed. After 6‐weeks of ETOH feeding there were still no differences in circulating CTRP2 or CTRP3 levels, however, adiponectin and CTRP1 levels were both increased. These results indicate that long‐term alcohol consumption effects adipokine secretion in a specific manner. Further research will be needed to explore the physiological relevance of these findings, specifically, to determine if these changes are beneficial compensations to combat the negative effects of excessive alcohol consumption. Lastly, even though CTRP2 and CTRP3 levels were unaffected by chronic alcohol consumption, elevated CTRP2 and CTRP3 may still be beneficial in combating the progression of AFLD.

Support or Funding Information

This research was supported in part National Institute On Alcohol Abuse And Alcoholism of the National Institutes of Health under Award Number R03AA023612 and East Tennessee State University Research Development Committee (E82262).
Functional Expression of TRPV4 in the Mouse Colon
Authors: Poole Daniel , Rajasekhar Pradeep , Nowell Cameron , Christensen Anne , Fichna Jakub , Bunnett Nigel , Veldhuis Nicholas
Published: November 2023

Background and Aims

The Transient Receptor Potential (TRP) family of non‐selective cation channels allow cells to sense diverse physical and chemical stimuli, and also mediate or amplify the actions of many GPCRs. TRPs participate in many physiological and pathophysiological processes and are an emerging therapeutic target for pain and neurogenic inflammation. TRP vanilloid 4 (TRPV4) is activated by stimuli commonly present in the colon, including mechanical stimulation, lipid mediators and GPCR‐dependent signaling cascades. TRPV4 is upregulated in inflammatory bowel disease and may have a proinflammatory role in experimental colitis via a neurogenic mechanism. Although TRPV4 has important roles in colonic function, very little is known about where TRPV4 is expressed in the gut. This study examines novel non‐neuronal sites of TRPV4 expression in the colon and inflammation‐associated changes in TRPV4 signaling.

Methods

TRPV4 activity was detected by Ca2+ imaging of myenteric and submucosal wholemount preparations of mouse colon. Cellular identity was confirmed by immunofluorescence using established markers. Functional expression was characterized in relevant primary cells and cell lines in culture.

Results

Increased intracellular Ca2+ was detected in enteric glial cells, macrophages, and vascular and lymphatic endothelial cells in response to the selective TRPV4 agonist GSK1016790A (100nM). All responses to GSK1016790A were abolished by pre‐treatment with the TRPV4 antagonist HC‐067047 (10μM) and were absent in trpv4−/‐ tissues, confirming specificity. Identity of cells was confirmed by post‐staining with SOX10/GFAP, CD68/F4/80/CD169, CD31, and LYVE1/VEGFR3, respectively. Myenteric glial responses were characterized by transient oscillatory Ca2+ waves within a subset of glia that were attenuated in frequency by the gap junction inhibitors carbenoxolone and 43GAP26. Similar reductions in both the number and type of Ca2+ responses by glial cells were detected in tissue preparations from mice with TNBS colitis. Tissue‐resident macrophages exhibited marked morphological changes in response to TRPV4 activation. Direct activation was confirmed by Ca2+ imaging of isolated glial cells, macrophages (RAW264.7, resident, peritoneal and bone‐marrow derived macrophages) and primary human dermal lymphatic endothelial cells.

We have defined novel and previously unappreciated sites of functional TRPV4 expression in the colon. These findings differ from those reported using immunofluorescent detection and demonstrate TRPV4 function in cells potentially involved in colonic motility (macrophages, glia) and inflammation (vascular and lymphatic endothelia, macrophages). Thus, these findings have major implications for our current understanding of the proposed neurogenic role of TRPV4 in colonic inflammation and in intestinal motility.

Support or Funding Information

NHMRC Australia APP1083480
The Great Reveal: The Virtual Microscopy Database & How to Make It Work for You
Authors: Lee Lisa M.J. , Goldman Haviva M , Hortsch Michael
Published: November 2023

This session will introduce a new collaborative tool that will help teachers and researchers to adapt to the changing landscape of histology and pathology education. The use of virtual microscopy has now become the norm in many medical curricula. Numerous advantages of these programs over the optical microscope labs have been well documented in the literature. Unfortunately, the technological parameters, expertise and expense that are required to create virtual microscopy collections, often pose a barrier to the use of such a powerful resource. Funding from the AAA's Innovation Program and support from the AAA's Digital Histology Interest Group made the creation of the Virtual Microscopy Database (VMD) possible. The VMD is a centralized and comprehensive resource share site where educators and researchers from all over the globe can upload and/or download virtual microscope image files. The purpose of the VMD is to offer its users access to a wide selection of virtual images, thereby enhancing and promoting their educational and research endeavors. In this session, the VMD website will be introduced through a hands‐on demonstration. This session will feature a tour of the VMD's expanding image library and its features designed to promote communication and collaboration among its users. Guidelines for uploading and downloading digital files will be discussed along with recommended data file format, annotations, copyright considerations and use of the VMD resources under the conditions of a Creative Commons License. Lastly, preliminary analytics on the VMD web traffic, uploads, downloads, and resource usage will be presented.

By the end of this session, the attendees should be able to

create an account and become a member of the VMD,

gain access to the web tools including the virtual tissue library,

upload and/or download data files,

and explore opportunities for interinstitutional and interdisciplinary collaboration.

Support or Funding Information

American Association of Anatomists Innovations Program
Surgical Removal of Gut Bacteria Biomass Promotes Weight Gain via Suppression of Energy Expenditure
Authors: Pearson Nicole A , Riedl Ruth A , Atkinson Samantha N , Ollinger Tomye L , Burnett Colin ML , Edwards Robert A , Mokadem Mohamad , Kirby John R , Grobe Justin L
Published: November 2023

A role for gut microbiota in energy homeostasis has been supported by studies involving twins, fecal transplants, colonization of germ‐free animals, and antimicrobial treatments. Although these studies have documented qualitative changes in digestive efficiency and microbiota‐host communication, there have been few attempts to quantitatively assess the relative contributions of these processes. Therefore it remains unclear whether other energy balance mechanisms may also contribute to the observed effects of the gut microbiota upon host energetics. It has been estimated that bacteria contribute 1–3% of adult human body mass, and that bacteria metabolize energy at ~7 kcal/kg/hr; thus bacteria in a 90 kg man should utilize 150–450 kcal/d, which is the equivalent of 7–22% of a 2,000 kcal/d human energy flux. We therefore hypothesize that gut bacteria contribute a physiologically‐relevant fraction of the host's total energy expenditure, and that removal of bacterial biomass would lead to increased weight gain despite simultaneously reducing digestive efficiency. To test this hypothesis we surgically removed the cecum (which is filled with bacteria and accounts for ~1% of body mass in mice) from 13 week old female C57BL/6J mice, and serially assessed host energetics by bomb calorimetry for two months. Compared to sham surgery, cecectomized mice gained significantly more weight (at four weeks: sham n=9, +1.72±0.21 vs cecectomy n=9, +2.95±0.30 g, p<0.05). Animals appeared healthy and active, with no changes in grooming or other behaviors noted. No differences in food (2920x chow) intake behavior (3.54±0.28 vs 3.30±0.12 g/d, p=NS) were observed. As expected, cecectomy significantly reduced digestive efficiency (85.8±1.1 vs 82.4±0.9, p<0.05), but no difference in total caloric absorption was observed (13.71±1.23 vs 12.23±0.50 kcal/d, p=NS). Energy efficiency (weight gain per calorie absorbed) was significantly increased with cecectomy (4.31±0.59 vs 8.15±0.90 mg/kcal, p<0.05). Collectively, these data demonstrate an increase in weight gain after removal of gut bacterial biomass in mice, which occurred due to a major suppression of energy expenditure. Notably the weight gain‐resisting suppression of digestive efficiency was insufficient to offset the reduction in energy expenditure that also occurred with cecectomy, resulting in a net caloric retention and thereby excess weight gain. These data highlight a large, dominant, quantitative contribution of gut bacteria to total energy expenditure. Additional studies to assess the contribution of the gut bacteria to aerobic vs anaerobic energy expenditure are required.
Dietary Fat and Carbohydrate Content Modulate Energy Expenditure via Gut Bacteria
Authors: Riedl Ruth A , Burnett Colin ML , Pearson Nicole A , Atkinson Samantha N , Ollinger Tomye L , Silva Genivaldo GZ , Edwards Robert A , Mokadem Mohamad , Kirby John R , Grobe Justin L
Published: November 2023

Dietary composition impacts the composition of the gut microbiota, and consuming high caloric diets (either high fat, HFD, or high carbohydrate, HCD) result in increased weight gain. Previous studies have estimated that bacteria contribute 1–3% (~1–3 kg) of an adult human's body mass and that bacteria typically exhibit an ~7 kcal/kg/hr metabolic rate, which implies a total contribution of 150–450 kcal/d to the host's apparent energy expenditure. As gut bacteria live within a largely anaerobic environment, we hypothesize that the biomass and composition of the gut microbiota contribute to whole‐animal energy homeostasis through anaerobic resting metabolic rate (RMR). Subsequently, we hypothesize that that HFD and HCD contribute to excess weight gain through the modulation of the biomass and composition of the gut microbiota and thus anaerobic RMR. Wildtype C57BL/6J mice were grown to 12 weeks of age on standard chow (Teklad 7913 or 2920x) before remaining on chow or switching to a HFD (45% kcal from fat) or HCD (70% kcal from sucrose) for one week. Mice were then anesthetized with ketamine/xylazine and examined for total (aerobic + anaerobic) RMR by direct calorimetry before and after acute cecectomy. Direct calorimetry methods were required, as conventional methods such as respirometry are blind to anaerobic processes. Mice fed HFD and HCD exhibited excess weight gain (7913 n=23, 25.86±0.37g; 2920x n=29, 25.82±0.34; HFD n=26, 27.97±0.36 p<0.05; HCD n=25, 27.16±0.37 p<0.05 grams). Cecum masses were significantly smaller in HFD and HCD groups (7913, 0.35±0.01; 2920x, 0.41±0.01; HFD, 0.20±0.01 p<0.05; HCD, 0.21±0.01 p<0.05 gram). Baseline total RMR was significantly suppressed by HCD (7913, 0.117±0.003; 2920x, 0.117±0.003; HFD, 0.116±0.003; HCD, 0.105±0.003 p<0.05 kcal/hr, ANCOVA‐corrected). Cecectomy, as an index of the RMR contribution of gut bacteria, had no effect in HCD mice (0.001±0.004 kcal/hr, p<0.05 vs all) but suppressed RMR in 7913 chow (−0.008±0.003) and HFD groups (−0.010±0.005) and even more so in the 2920x chow group (−0.019±0.005, p<0.05 vs all). Collectively these data demonstrate that HCD significantly suppresses total baseline RMR, that HFD and HCD both reduce the mass of the cecum and its contents, and that while HCD suppresses the RMR contribution of gut bacteria, soy‐free 2920x chow increases the RMR contribution of gut bacteria. These findings highlight the significant role of the gut microbiota in total energy expenditure and the important modulatory effects of diet upon this function.
HMGB2: A Novel Regulator and Potential Therapeutic Target for Liver Fibrosis
Authors: Huang Yi , Yang Zhihong , Shin Dong‐Ju , Keshipeddy Santosh K , Wright Dennis , Costa Antonio , Burgess Diane , Wang Li
Published: November 2023

Background and Aim

High mobility group box 2 (HMGB2) is a member of the non‐histone chromosomal high mobility group protein family. Liver fibrosis is characterized by the excessive deposition of the extracellular matrix proteins largely produced by activated hepatic stellate cells (HSCs). The current study aimed at elucidating a novel functional role of HMGB2 in hepatic fibrogenesis.

Methods

Liver fibrosis was induced by CCl4 in C57BL/6J mice. Overexpression of Hmgb2 in liver was produced by AAV8‐Hmgb2, whereas loss of function studies were performed in HMGB2−/− mice. HMGB2 inhibitor Inflachromene (ICM) and liposome‐shHMGB2 (lipo‐shHMGB2) were used to reverse liver fibrosis. Other methods: liver histology, immunohistochemistry (IHC), qPCR, Western blots, Co‐immunoprecipitation (Co‐IP), and primary stellate cell (HSC) culture.

Results

Hepatic HMGB2 expression was high during the embryonic stage but its level drastically decreased in adult liver, as revealed by RNA‐seq. However, the HMGB2 gene was reactivated in CCl4‐induced fibrotic liver in mice and in human fibrotic and cirrhotic liver. Overexpression of HMGB2 initiated fibrogenesis and augmented the effect of CCl4 as determined by Masson Trichrome staining. In contrast, liver fibrosis was prevented in HMGB2−/− mice. Plasma ALT levels were elevated in AAV‐HMGB2 mice and by CCl4 and were diminished in HMGB2−/− mice. Major fibrosis markers were markedly activated by HMGB2. HMGB2 protein expressed by AAV8‐HMGB2 was mainly observed in hepatocytes and HSCs, whereas the majority of endogenous HMGB2 protein induced by CCl4 was found in HSCs. Primary HSCs were culture‐activated as monitored for morphologic changes that are characteristic of transdifferentiation as well as induction of GFAP. As noted, HMGB2−/− HSCs showed impaired transdifferentiation and diminished activation of α‐SMA, AKT and ERK signaling. We introduced lipo‐shHMGB2 to knockdown the endogenous HMGB2 induced by CCl4 and observed a marked reduction in liver fibrosis. Intriguingly, mice treated with a small molecule inhibitor of HMGB2 ICM showed improved liver gross morphology and were prevented from developing liver fibrosis. This was accompanied by the decreased plasma ALT levels and diminished HMGB2 protein. Treatment of ICM in LX2 cells induced HMGB2 protein cytoplasmic localization and degradation, which was associated with its decreasing CCl4‐induced HMGB2 phosphorylation status.

Conclusion

HMGB2 is a novel regulator of liver fibrosis. Diminishing HMGB2 expression by ICM or lipo‐shHMGB2 provides a promising therapeutic strategy to prevent or reverse liver fibrosis.

All authors have nothing to disclose.

Support or Funding Information

Grant support: L.W. is supported by NIH R01DK104656, R01DK080440, R01ES025909, R21AA022482, R21AA024935, VA Merit Award 1I01BX002634, and P30 DK34989 (Yale Liver Center, Michael Nathanson).
High Fat Diet Impacts Colonic and Adipose Tissue Differently in Female and Male Sprague Dawley Rats
Authors: Sambolin‐Escobales Lubriel , Rodriguez Yarelis , Cruz‐Rentas Myrella Liz , Appleyard Caroline , Chompre Gladys
Published: November 2023

Introduction

Obesity has been associated with a variety of metabolic disorders such as cardiovascular diseases, hyperlipidemia, and diabetes among many others. Also, high fat diet (HFD) is associated with increased inflammation of the intestinal epithelial barrier. The inflammation might cause disruption of the integrity of the tight junctions of the epithelial barrier increasing intestinal permeability. Previous studies in our lab found higher macroscopic score and microscopic score in the colon, and reduced levels of tight junctions of male rats fed with a high fat diet (HFD) when compared to the control. However, the relation between sex differences consuming HFD in colonic macroscopic and microscopic score has not been studied well. We hypothesized that administration of a HFD will cause damage to the colon tissue, which may be gender dependent.

Research Design

male and female two‐month old rats were fed either a HFD (60% fat) or a LFD (10% fat) for 8 weeks. We measured the kilocalories per gram consumed every week and the absolute weight daily. After 60 days, rats were euthanized to examine adipose tissue and the colonic tissue for damage, macroscopically and microscopically.

Results

We found an increased ingestion of kilocalories per gram in the HFD group compared to the LFD (p<0.05), in both females and males. Both groups showed an increase in the absolute weight of the HFD, however there are no differences in gender. Moreover, both groups, female and male in HFD show higher macroscopic score (p<0.05) than the control group, however there is no significance in the colonic microscopic damage. On the other hand, male HFD group shows significant difference in colonic hyperemia compared with the female HFD (p<0.05). Further, the results did not show significant differences in the mesenteric fat weight or colonic microscopic damage score. In conclusion, the colonic tissue damage shows sex difference colonic macroscopic tissue damage but not microscopically. However, the hyperemia mechanisms behind the tissue damage require further investigation. This study helps us to understand the possible structural consequences in the colon following consumption of a high fat diet in sex differences.

Support or Funding Information

Supported by NIGMS/INBRE P20 GM103475‐14 and Ponce Health Sciences University Foundation.
Arrowhead Variation of the Anterior Digastric Musculature
Authors: Holmes J. Scott , Rickards Allen A. , Swearingen Jordan V , Miller Kyle D , Mangus Kelsey R. , Zdilla Matthew J. , Lambert H. Wayne
Published: November 2023

The submental musculature is important in numerous head and neck surgeries including rhytidectomy, the submental artery flap, and anterior digastric muscle transfer. Variations can lead to complications during surgery and may necessitate appropriate contingency plans when encountered. Further, variations of the anterior digastric musculature are common; however, few attempts have been made to categorize commonly occurring anterior digastric variations. This report documents the prevalence of a variation of the anterior digastric musculature previously thought to occur as an entirely unique variation. The variation appears as sheet‐like bilateral anterior digastric musculature variations converging at the mylohyoid raphe to form an ‘arrowhead.’ The results of this study demonstrate that the variation is not completely unusual. Surgeons should be aware of the potential for an arrowhead variation of the anterior digastric musculature to contribute to difficulty in regional surgeries. Understanding the anatomy and prevalence of arrowhead anterior digastric variations is of particular importance because current screening methods have not been demonstrated to identify such sheet‐like variations of the submental musculature.

Support or Funding Information

Funding for Holmes JS, Rickards AA, Swearingen JV, and Miller KD was provided by the WVU Initiation to Research Opportunities (INTRO) Summer Research program. Funding for Mangus KR was provided by the WV Research Challenge Fund [HEPC.dsr.14.13].
Rare Muscular Variations Identified in a Single Cadaveric Upper Limb: A Four‐headed Biceps Brachii and Coracobrachialis Brevis Muscle Variant
Authors: Moore Colin W , Rice Charles L
Published: November 2023

Introduction

Supernumerary, or accessory, heads of the biceps brachii are variations associated with the biceps brachii and can vary in number and location in the arm. Variations in other arm muscles, such as the coracobrachialis, can accompany variations in supernumerary biceps brachii musculature. Testut (1899) described two classes of anatomical variations associated with the coracobrachialis muscle: the coracobrachialis longus and coracobrachialis brevis. While they share a common origin at the coracoid process, the coracobrachialis longus and brevis are differentiated by their insertions at the medial epicondyle, and the surgical neck of the humerus, respectively. The objective of this study is to provide a comprehensive description of two rare variant muscles identified in a single cadaveric upper limb: a four‐headed biceps brachii and the tendinous elevator of the latissimus dorsi, a rare coracobrachialis brevis variant.

Methods

The anatomical variations were identified during routine dissection of the brachial plexus of a left upper limb from an 83‐year old male cadaver. Use of cadaveric material for research purposes was approved by the local research ethics council in the Department of Anatomy & Cell Biology at the University of Western Ontario (REF#: 21082015).

Results

We observed a four‐headed biceps brachii muscle consisting of both an infero‐medial and infero‐lateral head both originating from the humeral surface. The humeral heads shared a common insertion with the biceps brachii tendon. The tendinous elevator of the latissimus dorsi originated from the coracoid process and inserted on the anterior surface of the latissimus dorsi tendon. A thick fascial structure, considered to be an ancestral remnant of the dorsal epitrochlearis muscle, extended from the latissimus dorsi tendon to the fascia covering the long head of the biceps brachii. Furthermore, an accessory brachialis muscle was also identified in this cadaveric specimen. A variant innervation pattern consisting of a communicating branch between the median and musculocutaneous nerves was also observed.

Conclusion

These anatomical variations are clinically relevant to surgeons and radiologists as they have potential to compress neurovasculature in the shoulder and arm. Supernumerary heads of the biceps brachii could complicate bone fracture injuries and, subsequent, surgical interventions by causing unusual fracture patterns of the humerus due to their size, orientation and forces produced by these muscles. Furthermore, coracobrachialis brevis variants have been associated with chronic shoulder pain in some individuals. The variants identified here are considered rare, and their co‐occurrence in a single upper limb has not been documented in the literature to our knowledge.

Support or Funding Information

Supported by NSERC
Lymph nodes of the level VI: anatomic study of lymph nodes located between the recurrent laryngeal nerve and the right common carotid artery
Authors: Saleh Samir , Hojaij Flávio , Camargo Cristina , Itezerote Ana Maria , Andrade Mauro , Akamatsu Flávia Emi , Jacomo Alfredo Luiz
Published: November 2023

Thyroid carcinoma is the most prevalent endocrin malignant neoplasm and lymphatic metastasis are common, mostly to lymph nodes of the ipsilateral central compartiment, in level VI, such as the paratraqueal and the pretraqueal lymph nodes. However, there is a specific area, not previously described that should be considered when performing radical neck lymph node resection.

In this anatomical study we described the region located among the right recurrent laryngeal nerve, right common carotid and right inferior thyroid artery. A surgical approach to this area is likely to cause more morbidity due to the proximity to the recurrent nerve. Also we compared anthropometric and demographic data with the presence of lymph nodes

We found lymph nodes in 22/32 individuals (68,75%); number of lymph nodes ranged from 0 to 6. In those cadavers which lymph nodes were found, the average was 1,65 ± 0,29 lymph nodes.

We found a positive correlation between There are lymph nodes in corpses classified as (não tem esta expressão em inglês, peça para o Samir achar o sinônimo)by accurate Ficher's Test(p= 0,03) and of the white race by accurate Ficher's Test(p=0,04). BMI was not related to the presence of lymph nodes, by Spearman's correlation test(p=0,461).
A Case Report and Proposal for the Systematization of Axillary Arch Muscles
Authors: Miller Joseph M. A. , Trelease Robert
Published: November 2023

A variety of axillary arch muscles have been reported with wide range of frequency of occurrence over the course of more than two centuries. Frequencies for the general incidence of axillary arch muscles have been documented in a general way, without differentiating among the variant types. Here we describe a new case of axillary arch muscle and propose a framework for classification of such muscles based on their origins, insertions, and innervations. During the dissection of the back, thorax, and axillary regions for a gross anatomy course for first year dental students, we identified a single axillary arch muscle on the left side of an 82 year old, Caucasian male cadaver. It originated from the lateral aspect of the superior lateral border of latissimus dorsi, extended through the axillary fascia, crossing anterior to the axillary sheath to insert on the superior brachial fascia, and tendon and fascicles of the deep distal aspect of the sternocostal head near its insertion. The muscle appeared to be innervated by ramifying proximal fibers of the thoracodorsal nerve. We saw no evidence of innervation by lateral or medial pectoral nerves or intercostobrachial nerve, all of which were a considerable distance from the muscle. In the literature, a wide range of axillary arch muscle variants has been variously described (a.k.a. as Langer's muscle, achselbogen muscle, and axillopectoral muscle) in an unsystematic way. We propose a classification of axillary arch muscles which categorizes these muscles into two types: Category I – latissimus dorsi origin, and Category II – non‐latissimus dorsi origin, and a number of subtypes based on insertion and innervation. Bergman et al. (1988) and other authors have noted different variants of latissimus dorsi origin arch muscles (our “Category I”) that varied in their insertion, for example, on the pectoralis major or its tendon, coracobrachialis, deep brachial fascia, with innervations including the medial or lateral pectoral nerves, thoracodorsal nerve, or intercostobrachial nerve. We provide an additional logical framework to designate these subtypes according to insertion and innervation. This classification scheme will help researchers catalog frequency of occurrence more precisely for the various types of axillary arch muscles.
Positional Variation of the Mandibular Foramen in African‐American Versus Caucasian Populations of Male and Female Human Skulls
Authors: Bee Mary Tracy , Aljerdi Ibrahim , Ciavaglia Marco , Elturk Adam , Barton Scott T
Published: November 2023

The mandibular foramen is an opening on the medial surface of the mandible, through which the inferior alveolar nerve passes. This nerve is targeted when anesthetizing the lower jaw, as required in many dental procedures. Our research investigated variability in the position of the mandibular foramen in male and female populations, as well as in Caucasian and African‐American populations. One hundred skulls from the Hamaan‐Todd collection at the Cleveland Museum of Natural History were digitally photographed and analyzed. Preliminary results do not identify a significant difference in the position of the foramen between males and females (p>0.10). However, a significant difference in the antero‐posterior position of the foramen in Caucasian and African‐American populations was identified (p<0.05). This has great clinical relevance as it may result in variable treatment and positioning of anesthesia needles in patients of different races.
Arteries of the skin. Anatomical study with guided CT scan dissections of the legs
Authors: Settembre Nicla , Bouziane Zakaryiae , Labrousse Marc , Braun Marc , Malikov Sergueï
Published: November 2023

INTRODUCTION

All surgical intervention need skin incision. Section of afferent vessels can cause skin necrosis.

The knowledge of skin vascularization can be helpful for surgeons to avoid complications.

The most important study on the arteries of the skin was performed in 1936 by Salmon. He performed dissection associated to radiography of the skin. This technique that was innovative at the time presented some limits and many questions remained unsolved.

Thanks to the new imaging technology (Hight resolution CT scan) associated to the dissections of the specimens we can obtain more data about arteries of the skin.

The aim of our study was to demonstrate the feasibility of guided CT scan dissections of the arteries of the skin.

MATERIALS AND METHODS

In 10 cadaver dissections of the lower extremity were performed.

A barium sulfate suspension (Micropaque®) with colored liquid latex (25%: 75%) was injected under low pressure via femoral artery. Two days after the injection, a CT scan of the specimen was performed using a 64‐row MDCT (Lightspeed, General Electric Healthcare, Milwaukee, USA). Image processing and compilation of MDCT data were used to reconstruct the images in curvilinear two‐dimensional modes: multiplanar reconstruction (MPR) and voluminal surface three dimensional modes: maximum intensitity projection (MIP).

As a second step we dissected the arteries and marked the skin vessels guided by the CT images MPR and MIP.

RESULTS

The CT scan of the legs allowed us to identify the principal arteries of the skin and to planify the dissection.

The guided CT dissection allowed us to performed the dissections paying attention to the afferent arteries et to show the course of the vessels in order to avoid a bad manipulation of the specimens.

CONCLUSIONS

The guided CT scan dissections of the legs is faisable and can be helpful for the study of skin arterial network with 3D visualization of afferternt arteries.

Support or Funding Information

No funding for this study
Development and Structure of the Chorioallantoic Membrane of the Ostrich, Struthio camelus Egg
Authors: Maina John N , Willoughby Bronwyn
Published: November 2023

In amniotic eggs, the chorioallantoic membrane (CAM) is formed by fusion of the allantoic‐ and the chorionic membranes. Because in the cleidoic egg the CAM provides O2 and nutrients to the developing embryo, it is analogous to the placenta of mammals. Since the needs for nutrients and O2 increase with embryonic development, we speculated that surface area and the vascularization of the CAM should increase with incubation time. The CAM is very instructive model for the study of angiogenetic mechanisms, especially in cancers and other diseases and conditions that affect the hemopoietic system. In birds, the development and structure of CAM has mostly been studied in the domestic fowl (Gallus gallus variant domesticus). Here, the CAM of the egg of the ostrich (Struthio camelus), the largest extant bird that weighs as much as 150 kg, lays the largest egg that may weigh as much as 1.5 kg, has one of the longest incubation periods of 40–42 days and one having particularly poor hatching success was studied. Seven ostrich eggs were weighed and incubated an Inco Term Incubator under a temperature of 36.3°C and a relative humidity 40%. The eggs were manually rotated at least 3 times a day to avert adhesion of the CAM to the internal shell wall. At days 14, 16, 21, 25 and 28, at least one egg was removed from the incubator, the shell removed and the CAM carefully laid out flat. Its surface area was determined using a quadratic lattice grid with squares of known areas. Tissue samples taken from different regions of the CAM and fixed in 2.5% glutaraldehye buffered in sodium cacodylate (osmolarity 350mOsm; pH 7.4) for light‐ and scanning electron microscopy. The surface area and the vascularity of the CAM increased greatly with the incubation time. The blood capillaries budged towards the inner shell wall. Because of the large size of CAM of the ostrich, it is more convenient to use in study of normal and abnormal vascular development. Its functional design may explain the particularly low hatchability of the ostrich egg.

Support or Funding Information

National Research Foundation of South Africa