bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Rapamycin‐Insensitive mTOR Signaling in the Regulation of Muscle Protein Synthesis in a Rat Model of Resistance Exercise
Authors: Ogasawara Riki , Suginohara Takeshi 
Published: November 2023

Resistance exercise (RE) activates signaling by the mammalian target of rapamycin (mTOR), and it has been suggested that rapamycin‐sensitive mTOR signaling is necessary for the increase in muscle protein synthesis (MPS) after RE. However, recent studies have reported that rapamycin does not completely inhibit the RE‐induced increase in MPS, suggesting that rapamycin‐sensitive mTOR‐independent (rapamycin‐insensitive mTOR and mTOR‐independent) mechanisms contribute to this event. The aim of this study was to investigate whether rapamycin‐insensitive mTOR signaling plays a role in the regulation of RE‐induced increase in MPS. The right gastrocnemius muscle of male Sprague‐Dawley rats aged 11 weeks was isometrically contracted via percutaneous electrical stimulation (100Hz, 5 sets of ten 3‐s contractions, 7‐s rest between contractions, 3 min rest between sets), while the left gastrocnemius muscle served as a control. Placebo, allosteric mTOR inhibitor rapamycin, or ATP‐competitive mTOR inhibitor AZD8055 was injected intraperitoneally 1 h before RE. Muscle samples were obtained 1 and 6 h after a bout of RE. RE increased MPS (measured by) at both time points after RE in placebo group. Rapamycin completely inhibited RE‐induced MPS 1 h, but not 6 h, after RE. On the other hand, AZD8055 completely inhibited RE‐induced MPS at both time points after RE. The phosphorylation of p70S6K at Thr389 and 4E‐BP1 at Thr37/46, which are downstream targets of mTORC1, was sensitive to both rapamycin and AZD8055. However, inhibition of 4E‐BP1 phosphorylation was more pronounced by AZD8055. Moreover, only AZD8055 inhibited the phosphorylation of Akt at Ser473, a downstream target of mTORC2. We conclude that RE‐induced increase in MPS is mTOR signaling‐dependent process, and furthermore, both rapamycin‐sensitive and ‐insensitive mTOR signaling regulate this event.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant No. 267028.
Deficiency of the intermediate filament syemin causes abnormalities in striated muscle and reduces bone mass
Authors: Garcia‐Pelagio Karla P. , Moorer Megan , Buo Atum , Chen Ling , Stain Joseph , Bloch Robert 
Published: November 2023

A large number of diseases ranging from skin disorders, to premature aging, to skeletal and cardiac myopathies are usually associated to mutations in genes encoding intermediate filament (IF) proteins, but synemin presence and function has not been described in skeletal tissue. IFs associate with the contractile machinery and costameres of striated muscle and with intercalated disks in the heart. It also acts as an A‐kinase anchoring protein (AKAP). We study the role of synemin in skeletal and cardiac muscle, and in bone by examining adult mice null for synemin (synm −/−). Our major finding in synm −/− mice are that: 1) Cardiac muscle shows left ventricular remodeling, contractile dysfunction and hypertrophy suggesting a mixed cardiomyopathy. 2) They present a mild skeletal muscle phenotype, a reduction in tension consistent with an increase in sarcolemmal deformability; and the organization of proteins associated with the contractile apparatus and costameres is not significantly altered and, 3) The presence of osteopenia including more than a 2‐fold reduction in trabecular bone and a reduction in cross sectional area. In total, these data suggest an important role for synemin in striated muscle and bone physiology.Support or Funding InformationSupported partially by APS‐Physiological Genomics Fellowship and UNAM‐PAPIIT (IA209016) to KPGP; NIH to JPS (R01‐AR063631), and RJB (R01 AR 055928); to NIA to AMB (F31‐AR064673)
Anabolic response with higher protein intake is largely achieved through suppression of protein breakdown in older adults
Authors: Kim Il‐Young , Shin Yun‐A , Schutzler Scott , Azhar Gohar , Ferrando Arny A , Wolfe Robert R 
Published: November 2023

Our recent metabolic study demonstrated in young healthy adults that whole body net protein accretion was greater with ingestion of a mixed meal containing ~70g vs. ~40g protein, the latter of which has previously been shown to stimulate a near maximal synthetic response in muscle. To test this relationship in aging adults, we determined whole body protein kinetics in eight older adults (69±5y, 83±14kg, 27±10kg/m2) with a crossover design in the fasted state and following ingestion of 35g (moderate protein, or MP) or 70g (higher protein, HP) protein in mixed meals. Whole body protein kinetics [i.e., protein synthesis (PS), breakdown (PB), and net balance (NB)] (mg/kg LBM/min)] were expressed as changes from fasted to fed states. Feeding resulted in positive NB at both levels of protein intake (for all; p<0.0001) but to a greater extent with HP (p<0.0001). NB was increased primarily through a greater reduction in PB (p<0.0001) and to a lesser extent the stimulation of PS (p<0.01). The increase in NB in the MP group was entirely due to a suppression of breakdown, as synthesis was not stimulated above the basal state (p>0.10). Importantly, linear relationship was observed between NB and the amount of protein intake (g/kg LBM) per meal (r = 0.997, p<0.0001). In conclusion, as in the healthy young adults, we found in older adults that the whole body anabolic response increases linearly with increasing amount of dietary protein without showing a sign of plateau, largely through a greater suppression of protein breakdown.Support or Funding InformationThe project was financially supported by Award Number UL1‐TR‐000039 and KL2‐TR‐000063 from the National Center for Advancing Translational Science (NCATS).
Docosahexaenoic Acid (DHA), not Leucine, May Protect HepG2 Cells from Palmitate‐Induced Non‐Alcoholic Fatty Liver Disease
Authors: Baum Jamie I , Carroll Timothy G , Shouse Stephanie A 
Published: November 2023

Non‐alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States, affecting 70 million adults and ~3% of young children. NAFLD is characterized by an accumulation of fat in the liver cells that is not caused by alcohol. NAFLD is closely associated with obesity and insulin resistance, which are precursors for development of type 2 diabetes. Recent data suggests that the PPARs (PPARα and PPARγ may be connected to the development and progression of NAFLD, which make them potential biomarkers for treating and diagnosing NAFLD. Currently, there are several approaches to treating NAFLD, including nutrition therapy and specific food recommendations. Diets high in protein, high in the branched‐chain amino acid leucine, and diets high in polyunsaturated fatty acids, such as DHA, have been linked with weight reduction and improved insulin resistance. However, neither has been evaluated as a treatment for NAFLD. Therefore, the objective of this study was to analyze the ability of leucine and DHA to act either synergistically or alone to reduce markers of NAFLD using HepG2 cells treated with palmitate as an in vitro model. HepG2 cells (80% confluent) received one of 6 treatments for 48 hours: control, vector control, 0.75 mM palmitate, 5 mM leucine + palmitate, 0.1 mM DHA + palmitate, or leucine + DHA + palmitate. Lipid deposition and markers of energy metabolism were measured. Data was analyzed using one‐way ANOVA with P < 0.05 indicating significance. There was no effect of leucine on cellular lipid deposition. However, cells treated with DHA had significantly less lipid deposition compared to cells treated with palmitate or palmitate + leucine. Palmitate increased Tfam expression compared to controls, however, there was no further effect of leucine. Palmitate + DHA and palmitate + leucine + DHA significantly increased Tfam expression compared to control, palmitate and palmitate + leucine. Palmitate significantly lowered PGC1a and PPARg expression, however treatment with DHA further decreased PGC1α and PPARγ compared to controls and palmitate, alone. Preliminary data shows no treatment effect on SIRT1 or mTOR phosphorylation. Taken together, these data suggest that DHA, not leucine, has the potential to reduce markers of NAFLD in HepG2 cells.Support or Funding InformationArkansas Biosciences Institute. University of Arkansas State Undergraduate Research Fellowship.
Reduced energy expenditure and increased sleep time contribute to development of ovariectomy‐induced obesity in mice fed a high fat diet
Authors: Moak Sydney P. , Browning Jackson R. , Dai Xuemai , Hall John E. , do Carmo Jussara M. 
Published: November 2023

Loss of ovarian estrogen is associated with metabolic disorders, including central adiposity and insulin resistance. However, the diet‐dependent and independent mechanisms by which loss of ovarian function increases central adiposity and causes metabolic abnormalities remain unclear. In this study we examined if caloric intake, energy expenditure and sleep time are important contributors to development of ovariectomy‐induce obesity in mice fed a control or high fat diet (45%, HFD). Eleven female mice at 4 weeks were divided into two groups: Sham‐operated (n=4) and ovariectomized (OVX, n=7) groups. Mice were fed a control diet for 9 weeks and shifted to HFD for an additional 9 weeks. Food intake and body weight were measured daily and body composition was measured weekly by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), motor activity (MA), sleeping time and feeding behavior were monitored for 4 consecutive days at week 9 during control diet or HFD. OVX did not alter caloric intake (9.4±0.4 vs. 9.0±1.0 kcal/g/day), body weight (23.7±0.8 vs. 23.1±1.0 g) or body composition, MA (45.7±13 vs. 44.3±15 m/day), sleep time (4.6±0.5 vs. 4.1±0.7 hr/day based on 40 sec criterion) or fasting blood glucose (137±1.0 vs. 135±7 mg/dL), but slightly reduced EE (3.0±0.6 vs. 3.8±0.2 kcal/hr) and VO2 (1.1±0.1 vs. 1.4 vs. 0.2 ml/min) compared to Sham group. After HFD feeding, OXV mice had significantly greater weight gain (8.2±1.0 vs. 4.8±1.2 g, p<0.05), increased fat mass (12.3±1.1 vs. 8.4 ± 1.6 g, p<0.05), increased sleep time (15.4±1.6 vs. 11.4±1.4 hr/day based on 40 sec criterion, p=0.03), but similar caloric intake (12.8±1.0 vs. 14.1±1.4 kcal/g/day), lean mass (18.8±1.1 vs. 18.7±0.5 g), MA (45.4±5.2 vs. 67.6±20 m/day), fasting blood glucose (146±8 vs. 125±8 mg/dL) and reduced EE (3.3±0.4 vs. 5.5±0.2 kcal/hr) and VO2 (1.1±0.01 vs. 1.8±0.05 ml/min) compared to Sham group. These results suggest that OVX does not alter body weight homeostasis in mice fed a normal diet, but when combined with HFD reduces energy expenditure and increases sleep time without altering food intake or fasting glucose levels.Support or Funding Information(NHLBI‐PO1HL51971, NIGMS‐ P20GM104357 and U54GM115428)
The Link Between Obesity and the Expression of O‐linked N‐acetylglucosamine Transferase in Ictalurus punctatus
Authors: Abernathy Oaklee Layne , Spainhour Rebekah , Kobayashi Yass 
Published: November 2023

The obesity epidemic in the United States is a serious concern that has driven researchers to determine genetic mechanisms that may contribute to its development. Previous studies in mice have shown that O‐linked N‐acetylglucosamine transferase (OGT) may serve as a satiety factor responsible for controlling food intake and body weight. OGT appears to signal “fullness” in the brain, and decreased OGT expression leads to massive weight gain and development of an obese phenotype in mice. In channel catfish, genetic selection toward increased growth often leads to the increased accumulation of fats in the abdomen, suggesting that channel catfish can be used as a model organism to study obesity development in humans. Screening of the catfish genome database yielded four highly homologous OGT transcripts. Primers were designed to discriminate two major transcripts containing a fifty base pair insert from the other two transcripts. The nucleotide sequence of amplicon corresponding to OGT transcripts was highly similar (>80%) to those of other fish. Because OGT expression in channel catfish has not been previously studied, the OGT expression was examined in the cDNA of brain, spleen, trunk kidney, liver, Brockman's body, and muscle tissues of “normal” phenotype catfish using RT‐PCR. OGT expression was detected in all tissues and was expressed at various levels. Currently, we are using RT‐PCR to determine quantities of OGT in the tissues. In future research, we will compare OGT expression in obese phenotype catfish to normal phenotype catfish and determine if OGT expression is decreased in obese catfish.Support or Funding InformationSupported by the Kansas IDeA Network of Biomedical Research Excellence (P20GM103418)
Piece‐Meal: Food is more filling when cut into pieces
Authors: Tal Aner , Wansink Brian 
Published: November 2023

We wished to examine whether cutting food into several pieces led to its being rated as more filling. Satiety is driven by psychological, as well as physiological, factors (Wansink 2007; Redden and Galak 2013). If people think they ate a more substantial meal, they feel fuller (Wansink et al. 2010). Perceived quantity can influence psychological satiety (Redden and Galak 2013; Wansink 2007; Tal and Wansink 2014). Here, we wish to examine whether increasing the number of units in a meal by cutting a bagel into pieces increases reported satiety.Participants (N = 43) completed the study for credit in a behavioral lab. They were randomly assigned to one of three groups. The study was run in the afternoon. Groups alternated every half hour.All groups were served a mini‐bagel (approximately 42.5 grams) with cream cheese. One group received the bagel whole. The other two groups received the bagel cut into four pieces. For one of those group, the bagel pieces were kept together. For the other, the pieces were spread apart. Participants were instructed to eat the bagel in its entirety. They then reported on fullness on measures of hunger, fullness, and satiation, all reported on 9‐point likert scales, added up to a summary satiety score. Measures were taken pre and post consumption, allowing calculation of increase/decrease in satiation as our dependent measure.A follow‐up replication was conducted with a larger sample (N = 72). In the replication study, we examined moderation by liking for bagels, measured on a 9‐point likert scale.Satiety increased the most for the pieces‐together condition (4.77). Whole bagel participants had the second highest increase in satiety (3.75), while those with the pieces apart reported the lowest increase in satiety (2.18). The effect was significant at a .04: F(2, 41) = 3.26.In the replication study, the effect of condition was significant at a .02 level: F (2, 64) = 4.21. Those in the 4‐pieces condition reported a higher increase in satiety (3.29) relative to eating the bagel whole (2.63). Once again, bagel cut into four spread pieces led to the lowest increases in satiety (1.72). There was also a marginally significant interaction of liking and condition: F(2, 64) = 3.02, p = .056, with those expressing greater liking displaying weaker effects.Food is perceived as more filling when divided into several pieces. Spreading the food apart mitigates the effect. This is likely because food volume appears lower when spread out, creating an overall appearance of a smaller serving. This provides evidence that it is the number of units, rather than the filling of the plate (Wadhera et al. 2012), that leads to increased satiety. Cutting food to pieces can help consumers feel fuller with similar amounts of food. Knowledge of this effect can thus help reduce overeating and consequent obesity.
Neonatal Supplemental Oxygen Exposure Promotes the Development of Metabolic Disease in Adult Rats
Authors: Sturgeon Madison , Hoover Michael , Leuhrs Rachel , Vellookunnel Shilpa , Chandrasekar Shreya , Murphy Austin , Bates Melissa 
Published: November 2023

Premature infants frequently require supplemental oxygen to sustain life, but little is known about how supplemental oxygen administered during the critical developmental window after birth increases the risk of age‐related disease, including obesity and diabetes. We hypothesized that neonatal rats exposed to supplemental oxygen (OXY) would have impaired glucose tolerance and that they would develop a diabetes phenotype earlier than controls (CON), when offered a high fat diet. We used an established rat model of neonatal oxygen exposure (80% O2 for 8–14 days) and glucose tolerance was evaluated 14 days and 12 months post‐natally. To evaluate glucose tolerance, baseline blood glucose was measured after an overnight fast, followed by an intraperitoneal injection of concentrated glucose. Blood glucose was then measured 15, 30, 60 and 120 minutes post‐injection. In a second experiment, two month old OXY and CON rats were randomly assigned to an animal‐based fat diet (60% of calories from fat), or standard, low fat diet for ten weeks. At the beginning of the study and each subsequent week, glucose tolerance was measured. At 14 days and 12 months, OXY rats had higher blood glucose at 15 and 30 minutes compared to CON rats. OXY rats fed a high fat diet developed frank glucose intolerance after 4 weeks. Ten weeks of high fat diet had minimal effect on glucose tolerance in CON rats. Taken together, these data suggest that supplemental oxygen during the neonatal period may pre‐dispose the premature infant to the development of metabolic disease later in life.Support or Funding InformationThis work has been supported by funding from the University of Iowa's Department of Health and Human Physiology.
mTORC1 is Involved in the Regulation of Bardet‐Biedl Syndrome 1 (BBS1) Gene Expression
Authors: Guo Deng Fu , Bell Balyssa , Reho John J , Rahmouni Kamal 
Published: November 2023

The high prevalence of obesity is associated with increased health risks such as cardiovascular disease and diabetes. A combination of genetic and environmental factors such as availability of nutrition‐rich food contributes to the epidemic of obesity. Recent studies from our group have demonstrated the importance of hypothalamic BBS genes and the BBSome for the regulation of energy homeostasis. We hypothesized that regulation of BBS genes in the hypothalamus may be altered in diet‐induced obese mice. To test this, we investigated the expression of different BBS genes in the hypothalamus of mice fed with normal diet (ND) or 60% high fat diet (HFD) for 36 weeks. Expression of Bbs1 gene, but not Bbs2, Bbs4, Bbs5, Bbs6, Bbs7, Bbs8 and Bbs9, was significantly decreased in the hypothalamus of HFD fed mice vs. to mice fed ND, by qRT‐PCR (n=6 each, p<0.05). Additionally, we found that Bbs1 gene expression was significantly down‐regulated in the hypothalamus of mice fasted for 16 hrs compared to non‐fasted mice (n=6 each, p<0.05). To gain mechanistic insights, we used mouse hypothalamic GT1‐7 cells. Interestingly, we found that exposing GT1‐7 cells to nutrients (leucine (10 mM) or glucose (4.5 g/dl)), but not insulin (10 nM) for 16 hrs significantly decreased Bbs1 expression (n=3, p<0.05). Furthermore, intracerebroventricular injection of leucine (4 μg) decreased Bbs1 expression in the hypothalamus (n=3, p=0.053). Inhibition of the nutrient sensor, mTOR complex 1 (mTORC1) with rapamycin (100 nM) restored Bbs1 expression in GT1‐7 cells treated with leucine, implicating the mTORC1 pathway in the regulation of Bbs1 gene expression in GT1‐7 cells. Given that mTORC1 interacts with IKKα/β, we then tested IKK inhibition with BMS 345541 (500 nM). We found that this also restored Bbs1 gene expression in GT1‐7 cells treated with leucine. In contrast, NFkB p65 inhibition (NBP2‐29321, 25 mM) did not alter leucine‐induced down‐regulation of Bbs1 expression in GT1‐7 cells. We conclude that overnutrition‐induced decrease in hypothalamic Bbs1 gene expression may impair the BBSome function leading to the development of obesity.Support or Funding InformationThis project is supported by NIH and AHA grants to K.R.
Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency in Proopiomelanocortin (POMC) Neurons Attenuates Body Weight, Fat Mass and Liver Lipid Accumulation in Mice Fed a High Fat Diet
Authors: Aberdein Nicola , Wang Zhen , do Carmo Jussara M , Fang Taolin , Hall John E 
Published: November 2023

Leptin acts on the central nervous system (CNS) to reduce appetite and body weight, improve glucose regulation, and increase energy expenditure and sympathetic nervous system (SNS) activity. Central leptin has also been shown to exert antisteatotic effects on non‐adipose tissues. However, in severe obesity there may be resistance to leptin's anorexic, antidiabetic and antisteatotic effects but sustained effects to increase SNS activity, blood pressure (BP), and heart rate (HR). Our previous studies showed that POMC neurons are important for mediating the BP, HR and glucose effects of leptin but the role of POMC neurons in mediating leptin's effects on liver lipid accumulation remain less well defined. In this study we examined if deleting PTP1B, a negative regulator of leptin signaling, specifically in POMC neurons or in the entire forebrain, would protect mice against the adverse metabolic effects of a high fat diet (HFD). Male and female mice with forebrain (PTP1Bflox/flox/CamK2R5‐Cre) or POMC specific (PTP1Bflox/flox/POMC‐Cre) PTP1B deficiency and littermate controls (PTP1Bfox/flox) were fed a HFD from 6–20 weeks of age. Compared to PTP1Bflox/flox mice, mice with PTP1B deficiency in POMC neurons or in the entire forebrain had reduced body weight gain between 6 and 20 weeks of age when fed a HFD (Δ19.1 ±1.7g vs. Δ13.7±1.1g and Δ15.3±1.4g, respectively), and attenuated increase in fat mass (Δ13.3±1.2g vs. Δ7.3±0.7g and Δ10.2±1.0g, respectively). PTP1B deficiency attenuated food intake in forebrain specific PTP1B deficient mice compared to PTP1Bflox/flox and POMC specific PTP1B deficient mice (2.0±0.1g, 2.7±0.1g and 2.5±0.1 g, respectively). Glucose tolerance, expressed as area under the curve (AUC), was improved by PTP1B deficiency in forebrain and POMC specific neurons compared to PTP1Bflox/flox mice fed a HFD (AUC 19016±1172, 23207±1534 and 27561±3088, respectively). Liver fat mass, assessed by EchoMRI at 29±0.5 weeks of age, was reduced and liver lean mass was increased in mice with PTP1B deficiency in POMC neurons or in the entire forebrain (Fat: 8.8±1.8 and 6.0±3.3 mg/g, Lean: 93.6±2.8 and 97.2±5.6 mg/g, respectively) compared to PTP1Bflox/flox mice (Fat: 14.2±2., Lean: 79.4±10.3 mg/g), indicating a healthier liver profile. These findings indicate that PTP1B signaling in POMC neurons plays an important role in regulating body weight, fat mass, glucose tolerance and liver lipid accumulation in response to a chronic HFD but effects of PTP1B on food intake are mediated mainly in forebrain neurons other than POMC.Support or Funding Informationsupported by NHLBI‐PO1HL51971 and NIGMS P20GM104357.