bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Obese Female and Male SHHF/Mcc‐facp Rats with Antihypertensive Drugs, Nifedipine and Enalapril: Effects on Body Weight, Fat Distribution, Insulin Resistance and Systolic Pressure
Authors: Radin M. Judith , Chu Ying Yueh , Hoepf Toni M. , McCune Sylvia A.
Published: September 2012

Little is known about the effects of common antihypertensive drugs in obese, insulin‐resistant females. Nine‐month‐old obese female SHHF/Mcc‐fncp rats that received either nifedipine, a calcium channel antagonist, or enalapril, an angiotensin‐converting‐enzyme inhibitor, for three months were compared with untreated SHHF/Mcc‐facp rats (controls). After one month, nifedipine significantly decreased body weight in obese females compared to either enalapril or controls. After three months of treatment, total, abdominal, and subcutaneous fat masses were decreased in obese females given nifedipine compared to either enalapril or controls. Enalapril treatment was associated with a redistribution of fat mass from abdominal to subcutaneous depots. Nifedipine reduced plasma triglyceride and fasting glucose levels and improved insulin response to an oral glucose load in obese females, whereas enalapril did not appear to affect glycemic control. Systolic pressure was not significantly decreased until after two months of treatment with nifedipine or three months of treatment with enalapril in obese females and may have coincided with improvement in insulin‐resistance. Similarly, plasma atrial natriuretic peptide concentrations were significantly lower in obese females given nifedipine. To determine how obese males responded to a calcium channel antagonist, six‐month‐old obese male SHHF/Mcc‐facp rats were treated for three months with either nifedipine or placebo (controls). Nifedipine‐treated obese males showed a mild but significant decrease in weight gain that was due to a decrease in fat deposition in both subcutaneous and abdominal depots and systolic blood pressure was significantly reduced after one month of treatment. Nifedipine did not affect other plasma biochemical parameters in obese males. In conclusion, nifedipine improved systolic pressure and glycemic control in obese female SHHI;/Mcc‐facp rats, effects that may be associated with a marked loss in body weight and fat mass and improved lipid metabolism. Nifedipine‐treated obese males exhibited only a diminished weight gain that was not associated with changes in diabetic characteristics.
Effects of Dexamethasone on Primarily Cultured Newly Differentiated Rat Adipocytes from Different Adipose Tissue Regions
Authors: Yang Shumin , Xu Xuefan , Bjömrntorp Per
Published: September 2012

The effects of dexamethasone (dex) on newly differentiated adipocytes in primary culture derived from mesenteric, retroperitoneal, epididymal, and inguinal subcutaneous adipose tissues of male rats were studied. The degree of differentiation was similar in these adipose precursor cells derived from different regions as assessed by lipoprotein lipase (LPL) activity, an early marker of adipocyte differentiation. LPL activity was increased by addition of dex, and no differences in degree of activation were observed in cells from different adipose tissue regions. Development of both basal and isoproterenol‐stimulated lipolysis was also similar in adipose precursor cells from different adipose tissue regions. Dex addition enhanced the isoproterenol‐stimulated lipolysis with no regional differences. Studies of binding of [3H]‐dex showed no regional differences in either binding affinity or maximal binding capacity.

It is concluded that dex stimulates both LPL activity and lipolytic activity in newly differentiated rat adipocytes in primary culture. This seems, however, not to vary in magnitude in cells obtained from different adipose tissue regions. This might be due to the apparent similarity of number and affinity of glucocorticoid binding sites. Regional variations in glucocorticoid regulated LPL and lipolytic activity in adipose tissue might therefore not be due to inherent differences between adipocytes.
Time‐Dependent Effects of Progressive Gamma ‐Linolenate Feeding on Hyperphagia, Weight Gain, and Erythrocyte Fatty Acid Composition During Growth of Zucker Obese Rats
Authors: Thurmond Debbie C. , Tang Anna B. , Nakamura Manabu T. , Stern Judith S. , Phinney Stephen D.
Published: September 2012

Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma‐linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow‐up study, 16 obese (fa/fa) and 16 lean (Fa/Fa) 4‐week‐old male rats were randomized into 4 groups of 8 each and gavaged daily with soybean oil (SOY) containing 55% 18:2ω6 (an AA precursor) or GLA, using a progressive dose (≤ 5% of total calories) based on body weight. A defined diet with 11% of energy as SOY was fed ad libitum for 60 days. GLA obese had lower body weight (p<0.0001) and 60‐day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups. For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05). Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats. Erythrocytes collected at 15‐day intervals showed parallel increases in AA in both genotypes over time, suggesting normal AA availability during rapid growth. Thus, the reduced PL AA in the livers from the obese rats probably reflects impaired distribution in selected tissues rather than reduced hepatic production. Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity.
Feeding Response of Rats to No‐Fat and High‐Fat Cakes
Authors: Sclafani Anthony , Weiss Kerri , Cardieri Catherine , Ackroff Karen
Published: September 2012

The nutritional effects of high‐fat diets have been extensively studied in laboratory animals, but as yet few experiments have examined the feeding response of animals to newly developed fat substitutes. The present study used commercially available no‐fat (0% fat, 92% carbohydrate) and high‐fat (41% fat, 54% carbohydrate) cake to determine the effects of fat substitutes on food preference and caloric intake in rats. The first experiment showed that nondeprived rats found the high‐fat and no‐fat cakes equally palatable and highly preferred to lab chow. Food deprived rats, however, preferred the high‐fat cake to the no‐fat cake, which may be related to its higher caloric density. In the second experiment, rats fed high‐fat cake, in addition to chow, for 30 days consumed more calories and gained more weight than did rats fed no‐fat cake and chow. The no‐fat cake group, however, overate and gained more weight than chow‐only controls. The hyperphagic response to the no‐fat cake can be attributed to its carbohydrate content, moisture, and high palatability. Thus, removing fat from the cake reduced, but did not eliminate, its obesity‐promoting effect. Obviously, low‐fat foods must be consumed in moderation if used for weight control.
Effect of Ethnicity and Geographical Location on Body Weight, Dietary Restraint, and Abnormal Eating Attitudes
Authors: Wing Rena R. , Adams‐Campbell Lucile L. , Marcus Marsha D. , Janney Carol A.
Published: September 2012

Previous studies have examined the effect of ethnicity on obesity, concerns about shape and weight, and attitudes about eating. We hypothesized that geographical location would also influence these variables, and that students growing up in the northern part of the United States and attending northern colleges would differ from students from the South. To examine this, we studied a random sample of 275 African‐Americans (AA) and 224 white college students in the entering class of two northern colleges (University of Pittsburgh or University of Massachusetts) or two southern colleges (Augusta or Paine College). All subjects were weighed and completed the Revised Restraint Scale and the EAT‐26. AA women were heavier than white women, with no differences due to geographical location. Despite being thinner, white women reported more dietary restraint than AA women. This difference between AA and white women was apparent in both northern and southern college students. In contrast, geographical location was the strongest determinant of bulimic attitudes; both men and women at northern colleges reported higher bulimia scores than those at southern schools. Thus ethnicity appears to be a major determinant of body weight and attitudes about shape and dieting, whereas geographical location appears to exert greater influence on bulimic attitudes.
The Influence of Hydrocortisone (HC) on Differentiation of Adipose Tissue is Dependent on Fetal Age
Authors: Hausman Gary J. , Wright J. Thomas
Published: September 2012

Elevated serum hydrocortisone (HC) levels are associated with larger fat cells and elevated levels of Iipogenic and associated enzymes in late term pig fetuses from genetically obese dams. We have investigated the influence of HC status per se on these and other adipose tissue traits by chronically treating pig fetuses hypophysectomized (hypox) on day 70 with HC between either day 70 and 90 or 90 and 105 of gestation. Treatment with HC during both periods increased serum HC levels (P<.05) and increased fat cell size (P<.05) in the perirenal (PERI) and subcutaneous (SQ) depots, but failed to influence body weights, insulin‐like growth factor‐1 and insulin levels. Quantitative analysis of sections of PERI and SQ adipose tissue indicated that HC increased lipoprotein lipase (LPL), esterase and glucose‐6‐phosphate dehydrogenase (G6PDH) activities. The degree of esterase and G6PDH, but not LPL response to HC, was greater during the 90‐ to 105‐day period than during the earlier period. HC significantly increased lipid accretion only in the SQ depot between 90 and 105 days. Overall, HC significantly augmented hypox‐induced alterations in cellular and metabolic traits of developing adipose tissue. The general increase in fat cell size (21%) with moderate (SQ‐105d) or no (PERI‐90, 105d; SQ‐90d) increase in lipid accretion indicates that HC either did not influence or decreased apparent fat cell number. Regardless, these data indicate that changes in serum HC per se may account for adipose tissue traits that characterize fetuses from genetically obese dams.
Positive Modulation of the Adipoconversion of Adipoblasts Derived from Genetically Obese Rats by Sodium Butyrate
Authors: Gregoire Francine M. , Magrurn; Linda , Johnson Patricia R. , Greenwood MRC
Published: September 2012

Using a new serum‐free primary culture system, we have previously reported genotypic differences between adipoblasts derived from the epididymal adipose deposit of lean and obese 8‐week‐old Zucker and Wistar Diabetic Fatty (WDF) rats (15). In these strictly controlled culture conditions, obese‐derived adipoblasts expressed low levels of the late markers of differentiation (lipid accumulation, GPDH). In order to further characterize obese‐derived adipoblasts and analyze the critical relationship between growth and differentiation, growth arrest was induced in leanand obese‐derived cultures using sodium butyrate treatment. Addition of 2.5 mM sodium butyrate to the serum‐free medium from day 1 reduced markedly the growth of lean as well as obese‐derived cells. Adipoconversion of lean‐derived adipoblasts was not altered, similar levels of LPL and GPDH activities being obtained in control and butyrate‐treated groups. By contrast, a marked increase in both activities was observed in obese‐derived cultures, restoring the level of both markers of differentiation to the lean level. Similar results were obtained with adipoblasts derived from subcutaneous inguinal (ING) fat pad of obese Zucker as well as adipoblasts derived from ING and EPI fat deposits from obese WDF rats. Taken together, these results suggest that adipose deposits of these genetically obese rats contain a specific adipoblast population which differs from lean‐derived adipoblasts in respect to its adipoconversion capacity andlor its stage of commitment to differentiation.
A Role for Testosterone in the Maintenance of Seasonally Appropriate Body Mass but not in Lipectomy‐Induced Body Fat Compensation in Siberian Hamsters
Authors: Mauer Mary Margaret , Bartness Timothy J.
Published: September 2012

The purpose of this study was to test whether serum testosterone (T) concentrations characteristic of reproductively active, long‐day‐housed Siberian hamsters are necessary for compensatory increases in nonexcised fat pads following removal of epididy‐mal white adipose tissue (EWAT) and/or for the maintenance of seasonally appropriate body weights in these hamsters. Long‐day‐housed hamsters were castrated or left intact, sham or EWAT lipectomized, and given T or cholesterol (C) implants. All groups had ad libitum food access except for two castrated T‐treated groups that were pair‐fed to their C‐treat‐ed counterparts to control for effects of T on food intake. C‐treated castrates had decreased body weights compared with all other groups, suggesting a role of T in the maintenance of seasonally appropriate body mass. Since the T‐treated hamsters pair‐fed to these T‐deficient animals exhibited seasonally appropriate body weights and fat pad masses, T does not appear to affect these parameters through the modulation of food intake. All fat pads of C‐treated animals were smaller than those of ad libitum‐ or pair‐fed, T‐treated castrates; however, EWAT was the only fat pad that was smaller in the C‐treated sham‐lipectomized group than in gonad‐intact sham‐lipectomized hamsters. This result may indicate an enhanced sensitivity of EWAT to T. The effects of T on fat pad mass were not associated with proportionate changes in lipoprotein lipase activity, suggesting that the major effect of T on fat accumulation occurs through other mechanisms in this species. C‐treated lipectomized hamsters compensated for the body fat deficit 8 weeks after lipectomy via statistically nonsignificant increases in retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is necessary for maintenance of seasonally‐appropriate body weight, it is not necessary for fat pad compensation after EWAT lipectomy.
Effects of Testosterone on Triglyceride Uptake and Mobilization in Different Adipose Tissues in Male Rats in Vivo
Authors: Per Min , Björntorp Li
Published: September 2012

LI, MIN AND PER BJ4OURNTORP. Effects of testosterone on triglyceride uptake and mobilization in different adipose tissues in male rats in vivo. Obes Res. 1995;3:113–119.

The effects of testosterone (T) on uptake and mobilization of orally administered triglyceride were examined in male rats. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo. (U‐14 C) oleic acid in sesame oil was given by gastric gavage to male, sham operated, castrated and castrated + T substituted rats, and accumulation and half‐life of radioactivity measured. In castrated rats in comparisons with sham‐operated and castrated + T rats, serum T was absent, and body weight lower (P< 0.05 or 0.01), but adipocytes in retroperitoneal and mesenteric tissues became significantly heavier. Radioactivity (dpm/mg triglyceride) was higher, in retroperitoneal tissue at 4 hours, 7, 30 days, and in mesenteric tissue at 4 hours, and at 30 and 60 days after oral label administration (0.1 > p > 0.05 or P< 0.05), no differences were seen in epididymal or inguinal depots at 4 hours. When radioactivity was expressed per adipocyte, the castrated group showed significantly higher radioactivity when compared to sham and castrated + T groups at 7 and 30 days in retroperitoneal and at 60 days in mesenteric adipocytes (P< 0.05 or 0.01). Half life (T 1/2) of radioactivity was longer in mesenteric tissue in the castrated rats than the other two groups (sham group, 33 days ± 2; castrated group, 58 days ± 6; and castrated + T group, 39 days ± 3, P< 0.05), but there were no differences between groups in retroperitoneal adipose tissue. It was concluded that T exerts important, multiple effects on triglyceride storage and mobilization in adipose tissue, with regional differences between adipose tissues.
Relation of Body Fat Distribution to Reproductive Factors in Pre‐ and Postmenopausal Women
Authors: Troisi Rebecca J. , Wolf Anne M. , Manson Jo Ann E. , Klingler Kelly M. , Colditz Graham A.
Published: September 2012

TROISI, REBECCA J, ANNE M WOLF, JOANN E MANSON, KELLY M. KLINGLER AND GRAHAM A. COLDITZ. Relation of body fat distribution to reproductive factors in pre‐ and postmenopausal women. Obes Res. 1995;3:143–151.

The cross‐sectional relations of several reproductive characteristics with self‐reported waist‐to‐hip circumference ratio were evaluated in 44, 487 pre‐ and postmenopausal women 40 to 65 years of age who were free of cancer, cardiovascular disease, and diabetes. All results were adjusted for age, body mass index, cigarette smoking, physical activity, and alcohol intake. Current use of postmenopausal hormones was associated with a significantly lower waist‐to‐hip ratio than either past or never use independent of type of menopause (0.778 versus 0.784, p=0.0001 and 0.787, p=0.0001, respectively), although associations with type (unopposed estrogens versus combined estrogen and progesterone) and duration of hormone therapy were not noted. Waist‐to‐hip ratio did not differ between pre‐ and postmenopausal women, but demonstrated weak positive associations with age at menarche, parity, and age at first birth, and a weak inverse association with past duration of breast‐feeding. These data confirm relations of several reproductive factors and use of hormone replacement therapy with body fat distribution. Epidemiologic studies relating body fat distribution to disease outcomes in women should consider these factors as potential confounders.
Monoclonal Antibody‐Mediated Cytotoxicity of Adipocytes
Authors: Wright J. Thomas , Hausman Gary J.
Published: September 2012

Monoclonal antibodies (MAbs) raised against porcine adipocyte plasma membranes were used to demonstrate complement‐mediated cytotoxicity of adipocytes and preadipocytes in primary stromal‐vascular (SV) cultures. Five of the six MAbs tested significantly reduced the number of fat cell clusters in cultures maintained in medium supplemented with pig serum and dexamethasone (PS/DEX) but not in cultures supplemented with insulin, transferrin, and selenium (ITS). Neither MAb nor complement alone affected fat cell cluster number. Treatment of both ITS and PS/DEX cultures with pools of 2 or more MAbs, in combination with complement, eliminated fat cell clusters in all instances. Treatment of cultures prior to appearance of cells containing lipid demonstrated that preadipocytes, or adipose lineage cells, could also be eliminated by MAb/complement treatment. Finally, injection of young rats with a pool of three of the MAbs produced a 30% reduction in inguinal fat pad weight without affecting other tissues. Adipocyte/ preadipocyte‐depleted cultures can now be used as a model system to examine progression of cells through the adipose cell lineage at a time not previously possible with primary cells.
Body Habitus Changes Among Adult Males From the Normative Aging Study: Relations to Aging, Smoking History and Alcohol Intake
Authors: Grinker Joel A. , Tucker Katherine , Vokonas Pantel S. , Rush David
Published: September 2012

Body habitus changes among adult males from the normative aging study: relations to aging, smoking history and alcohol intake. Obes Res. 1995;3:435–446. The Normative Aging Study (NAS) recruited 2280 Boston area healthy males aged 21 to 80 in 1961 through 1970. Clinical exams have continued at 3‐ to 5‐year intervals. Obesity was not an exclusion criterion. Stability in weight and body habitus among 867 adult participants in the NAS was evaluated at 5‐and 15‐year follow‐ups. At study entry, age was linearly related to central adiposity [abdominal circumference (AC) and ratio of AC/Hip Breadth (HB)] throughout the entire age range (30 to 78 years) and linearly and quadratically related to weight (WT) and Body Mass Index (BMI) (kg/m2) with maximal values at age 50. Over 15 years, changes in adiposity were strongly related to age; the greatest increases were among those initially 30 to 44 years of age with decrements in several adiposity measures (BMI, AC) only among the oldest subjects (60+ at entry); significant quadratic effects of age for BMI (p<. 001), WT (p<. 02) and AC (p<. 01). There were major secular differences; men born later were heavier and fatter at the same ages as men born earlier. Men who gained (>1 BMI) were younger while men who lost (>1 BMI) had greater initial central adiposity than others. Smoking cessation was independently associated with increments in both central and peripheral adiposity. Moderate alcohol intake was associated with lower gains in AC/HB ratios at 15 years compared with little or high consumption. In general, aging was associated with trends towards central adiposity which tended to plateau or decrease at the oldest ages.
Multiple Serotonin Receptors: Opportunities for New Treatments for Obesity?
Authors: Dourish Colin T.
Published: September 2012

Recent progress in the molecular pharmacology of 5‐HT receptors and the development of selective ligands for various 5‐HT receptor subtypes has advanced our understanding of the role of 5‐HT mechanisms in the control of food intake and body weight The most intensively investigated 5‐HT receptor subtypes have been the 5‐HT1A receptor, the 5‐HT1B receptor andthe5‐HT2C receptor. The overall pattern of results to date suggests that selective 5‐HT2C agonists may be novel anorectic drugs and prove useful in the treatment of obesity. However, a number of issues remain unresolved, particularly regarding potential side‐effects, as the 5‐HT2C receptor agonist mCPP has been reported to induce anxiety and nausea in humans, actions that would clearly limit its therapeutic utility. In addition, the possible role of recently cloned 5‐HT receptor subtypes such as 5‐ht5,5‐ht6 and 5‐ht7 remains unexplored and the development of selective ligands for these sites has the potential to lead to new treatments for obesity.
Structure, Function, and Regulation of the Three β‐Adrenergic Receptors
Authors: Strosberg A. Donny
Published: September 2012

Three β‐adrenergic receptor subtypes are now known to be functionally expressed in mammals. All three belong to the R7G family of receptors coupled to G‐proteins, and characterized by an extracellular glycosylated N‐terminal and an intracellular C‐terminal region and seven transmembrane domains, linked by three exta‐ and three intracellular loops.

The catecholamine ligand binding domain, studied using affinity‐labeling and site‐directed mutagenesis, is a pocket lined by residues belonging to the transmembrane domains. The region responsible for the interaction with the Gs protein which, when activated, stimulates adenylyl cyclase, is composed of residues belonging to the parts most proximal to the membrane of intracellular loop i3 and the C‐terminal region.

The pharmacology of the three subtypes is quite distinct: in fact most of the potent β1/β2 antagonists (the well known β blockers) act as agonists on β3. The subtype is resistant to short‐term desensitization mediated by phosphorylation through PKA or βARK, in stark contrast to the β1 or β2 subtypes. Various compounds (dexamethasone, butyrate, insulin) up regulate β1 or β1 subtypes while down‐regulating β3 whose expression strictly correlates with differentiation of 3T3‐F442A fibroblasts into adipocytes, thus confirming that the expression of the three subtypes may each be regulated independently to exert a specific physiologic role in different tissues or at different stages of development.
Biochemical and Anthropometric Characterization of Morbid Obesity in a Large Utah Pedigree
Authors: Hunt Steven C. , Williams Roger R. , Adams Ted D.
Published: September 2012

A Utah family with morbid obesity was extended to include 122 persons in four generations for the purpose of characterizing anthropometric and biochemical variables in family members with and without morbid obesity. Seventy‐seven subjects had blood drawn for biochemical analyses. Of the 77 subjects, 12 were morbidly obese (≥44.5 kg or 100 pounds overweight), 20 were between 22.5–45.4 kg (50 and 99 pounds) overweight and 45 were less than 22.5 kg (50 pounds) overweight Sixty‐two randomly‐ascertained controls were used for comparisons of age‐ and gender‐adjusted study variables.

Morbidly obese subjects had mean body mass indices (BMI) of 41.0 kg/m2 (62 kg over ideal weight) compared to 25.3 kg/m2 (10 kg overweight) in the <22.5 kg family members (p<0.001). The <22.5 kg family members had lower BMI than the random controls (27.6 kg/m2, p<0.05), indicating clear bimodality of obesity within the pedigree. Percent body fat from bioelectrical impedance was 35% versus 24% in the morbidly obese and the <22.5 kg subjects, respectively. Ideal body weight was similar among the three pedigree weight groups. Hip and waist circumferences were much larger in the morbidly obese and the waist‐to‐hip ratio remained significantly greater in the morbidly obese subjects compared to the <22.5 kg group.

Morbidly obese subjects had elevated triglycerides and VLDL‐C levels, low HDL‐levels, and normal LDL‐C levels. Fasting insulin was the best predictor of morbid obesity of all biochemical and lipid measurements (odds ratio of 4.5). Fasting insulin levels and the insulin‐to‐glucose ratio were more than twice as high as control levels. Even after adjusting for differences in BMI, fasting insulin and the insulin to glucose ratio were elevated in the morbidly obese subjects indicating that insulin levels were inappropriately high for their weight compared to this relationship found in the other groups. Adjusted insulin levels for the 22.5–45.4 kg group were similar to controls, indicating insulin level was at the predicted level for their weight.

In conclusion, individuals with morbid obesity appeared to have greater insulin resistance than could be explained by their weight. CHD risk from elevated LD L‐C was not present, but CHD risk was increased by the so‐called multiple metabolic syndrome (insulin resistance, high triglycerides and low HDL‐C).
Treatment of Obesity by Personality Classification‐Oriented Program
Authors: Yoshida Sho , Murano Shunichi , Saito Yasushi , Inadera Hidekuni , Tashiro Jim , Kobayashi Junji , Tadokoro Naoko , Kanzaki Tetsuto , Shinomiya Masaki , Morisaki Nobuhiro , Ohono Kuniko , Ishikawa Yo , Shirai Kohji , Azuma Yukari , Kodama Kazuhiro
Published: September 2012

It is apparent that personality is related to the pathogenesis of obesity, and that understanding the personality of the patient may be a key to successful treatment of the disease. Using the Rorschach test and interviews by a psychiatrist, the types of personality were classified into four groups according to the healthiness of personalities. The judgment of healthiness was based mainly on the scores obtained from the Rorschach test This classification revealed that the occurrence of mental and physical symptoms during therapy with a very low calorie diet(VLCD)and subsequent rebound of body weight were more frequently observed in patients with relatively less healthy personalities. We used this classification to adapt our pro gram to treat obese patients. In this program, severe diet restrictions were applied to patients with relatively healthy personalities. These restrictions were applied with modifications to patients with less healthy personality, because severe restrictions would be possibly very stressful for them and would bring about an undesirable reaction. For strengthening the patients' motivation for therapy, the significance of body weight reduction was explained in different ways to patients with different types of personality. The target of body weight reduction, reward for patients with successful weight reduction, and the duration of therapy were setup differently for patients with different personalities types. The results showed that body weight rebound one or two years after treatment was reduced with the personality‐oriented therapy pro gram compared to that observed with the previous conventional therapies. Also, the incidence of psychological problems was remarkably decreased.
The Case For Randomized Clinical Trials on the Treatment of Obesity
Authors: Stern Michael P.
Published: September 2012

Some say that randomized clinical trials on weight loss are unnecessary (“the benefits are ‘obvious’”) and others say that such trials are not feasible because too few participants will succeed in maintaining weight loss. Although the intermediate term benefits of weight loss are beyond dispute (lowering of blood pressure, lipids, blood sugar, etc), there is no proof that these benefits will translate into long term benefits, i.e., lower rates of cardiovascular disease and/or lower overall mortality. While this extrapolation may seem obvious, the clinical trials' literature is full of unexpected, adverse side effects of theoretically appealing therapies (e.g., higher mortality with clofibrate and higher cardiovascular disease rates with estrogen treatment in men).

Although there is clearly a voluntary component to food ingestion, there are also powerful physiological forces at work which impact on energy balance. For example, individuals of similar height and weight may nevertheless have widely different daily energy expenditures and hence energy requirements. It has been shown in Pima Indians that those with low energy expenditure (i.e., those who are “fuel efficient”) are more prone to future weight gain than those with high energy expenditure. Also, reduced obese individuals have lower 24‐hour energy expenditure than individuals who are spontaneously at the same lean weight It appears that this deficit in energy expenditure may last for several years, if not longer, implying that reduced obese individuals must exercise far greater vigilance over their caloric intake than their spontaneously lean peers. If they allow themselves to ingest the same number of calories as the latter, they are likely to regain weight, thereby exposing themselves to charges of overeating, even though their caloric intake does not exceed that of the spontaneously lean!.

Epidemiologic data do not support a benefit of weight loss. Populations such as Mexican Americans, among whom obesity is more common than in the general population, do not have excess mortality past age 45. Life expectancy in the U.S. has improved steadily since the early 1970s, despite a rising prevalence of obesity. Lastly, prospective studies have suggested that people who lose weight die at a higher rate than those who maintain a stable weight. This effect persists even after controlling for latent, subclinical disease and cigarette smoking.

Although none of the above considerations prove that voluntary weight loss is bad, they indicate that this treatment should lose its hitherto privileged status and be subjected to the rigors of clinical trials as have been treatments for hypercholesterolemia and hypertension.
The Antiobesity Effect of Dehydroepiandrosterone in Castrated or Noncastrated Obese Zucker Male Rats
Authors: Taniguchi Susumu , Yanase Toshihiko , Haji Masafumi , Ishibashi Kotaro , Takayanagi Ryoichi , Nawata Hajime
Published: September 2012

Although antiobesity effect of dehydroepiandrosterone (DHEA) has been reported in rats, it remains unclear whether the effect is brought about by itself or mediated by sex steroids converted from DHEA in gonads. In the present study, to clarify this point, the effect of DHEA on growth in obese Zucker male rats was reevaluated under two conditions: with or without castration. Castration did not affect the pattern of growth curve of obese Zucker male rats. Three‐months treatment of castrated Zucker rats with 0.3% DHEA in the diet resulted in dramatic decrease of body weight gain in comparison to DHEA‐untreated and castrated rats. The degree of antiobesity effect of DHEA in castrated rats was almost same as that observed in non‐castrated rats. These results suggest that DHEA exerted its antiobesity effect by itself rather than through conversion to testosterone in testis.
The Association Among Fat Distribution, Physical Fitness, and the Risk Factors of Cardiovascular Disease in Obese Women
Authors: Tanaka Hiroaki , Kakiyama Tetsuji , Takahara Kazuko , Yamauchi Miyoko , Tanaka Mamoru , Sasaki Jun , Taniguchi Tetsuya , Matsuo Hisashi , Shindo Munehiro
Published: September 2012

The purpose of this study was to see whether fat distribution and physical fitness are independent risk factors of cardiovascular diseases in obese women. Seventy‐four obese women aged 19 to 65 years participated in this study. The data were collected on plasma lipid profiles, plasma glucose and insulin during an oral glucose tolerance test, blood pressure, fat distribution determined by the waist to hip ratio (WHR), total body fat determined by the hydrostatic weighing method and a direct measurement of blood lactate threshold. Significant correlations were found between WHR and plasma cholesterol (TC), plasma LDL cholesterol (LDL‐c) and LDL‐c to the plasma HDL cholesterol ratio (LDL‐c/HDL‐c), independent of age, percent body fat, and VO2 per lean body mass at blood lactate threshold (LT). On the other hand, LT was significantly related to the area under the curve of insulin during OGTT (insulin area) and DBP, independent of age, percent body fat, and WHR. In conclusion, both fat distribution and physical fitness are considered to be independently related to some important risk factors in obese women after adjustment for percent body fat.
Hypothalamic Neuronal Histamine Modulates Adaptive Behavior and Thermogenesis in Response to Endogenous Pyrogen
Authors: Sakata Toshiie , Rang Masahiro , Kurokawa Mamoru , Yoshimatsu Hironobu
Published: September 2012

Homeostatic involvement of hypothalamic neuronal histamine in adaptive behavior and thermogenesis was investigated when interleukin‐1β (IL‐1β), one of the endogenous pyrogens, was infused peripherally in rats. IL‐1β decreased food and water intake and elevated body temperature. Depletion of neuronal histamine in the hypothalamus induced by α‐fluoromethylhistidine, a suicide inhibitor of the histamine synthesizing enzyme histidine decarboxylase (HDC), attenuated the suppressive effect of IL‐1β on food intake, facilitated the inhibitory effect on water intake, and enhanced its thermogenic effect. Simultaneously IL‐1β increased activity of HDC and histamine‐N‐methyltransferase (HMT), a neuronal histamine catabolizing enzyme. Pretreatment with indomethacin completely blocked those increases in turnover of neuronal histamine induced by IL‐1β. Hypothalamic prostaglandin E2 (PGE2) activated by peripheral IL‐1β, but not peripheral PGE2, increased both activities of HDC and HMT. Ginsenoside Rg1 a major component of panax ginseng, modulated the suppressive effects of IL‐1β on ingestive behavior, resulting in a lowering of body temperature. The findings suggest that the effects of IL‐1β on ingestive behavior and thermogenesis may be modulated by dynamics of hypothalamic neuronal histamine through activation of hypothalamic PGE2 which is elevated by peripheral IL‐1β.
Energy Homeostasis, Autonomic Activity and Obesity
Authors: Scheurink Anton J.W. , Balkan Börk , Nyakas Csaba , van Dijk Gertjan , Steffens Anton B. , Bohus Béla
Published: September 2012

Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats. Particular emphasis is given to autonomic functioning and dysfunctioning in relation to the processes that are involved in the regulation of peripheral energy substrate homeostasis. It is concluded that alterations in autonomic regulation in obesity are determined by causal factors such as overeating, genetic make‐up, age and/or the duration of obesity.
A Major Gene for Resting Metabolic Rate Unassociated with Body Composition: Results from the Québec Family Study
Authors: Rice Treva , Tremblay Angelo , Dériaz Olivier , Pérusse Louis , Rao D.C. , Bouchard Claude
Published: September 2012

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat‐free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal — i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre‐ and post‐adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non‐Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.
Growth Hormone Treatment of Hypophysectomized Rats Increases Catecholamine‐induced Lipolysis and the Number of β‐Adrenergic Receptors in Adipocytes: No Differences in the Effects of Growth Hormone on Different Fat Depots
Authors: Yang Shumin , Björntorp Per , Liu Xinglu , Edén Staffan
Published: September 2012

Growth hormone (GH) has a lipolytic effect in adipose tissue but this effect may differ in adipose tissue from various fat depots. This latter possibility was investigated in the present study, in which the effects of GH in vivo on catecholamine‐induced lipolysis and the number of β‐adrenergic receptors in isolated adipocytes from different fat depots of hypophysectomized rats were investigated. Female and male Sprague‐Dawley rats were hypophysectomized or sham‐operated at 45 days of age. One week after the operation, hormonal replacement therapy with L‐thyroxine and hydrocortisone acetate was given. In addition, groups of rats were treated with GH (1.33 mg/kg per day, given as two daily subcutaneous injections). After 1 week of hormonal treatment, adipocytes were isolated from the parametrial, epididymal and inguinal fat pads, and glycerol release after catecholamine‐stimulation and 125I‐cyanopindolol binding were measured.

Hypophysectomy resulted in a marked decrease in the lipolytic response to catecholamines. GH treatment significantly increased catecholamine‐induced lipolysis with similar effects in adipocytes from parametrial or epididymal and inguinal fat depots in both female and male rats. There were no differences between norepinephrine compared with isoproterenol‐induced responses.

125I‐cyanopindolol binding was reduced after hypophysectomy and normalized by GH treatment, without differences between parametrial and inguinal adipose tissue regions.

We conclude that the lipolytic effects of GH in the rat may partly be mediated by a stimulatory effect on β‐adrenergic receptors in adipocytes. In addition, GH exerted similar effect on catecholamine‐induced lipolysis and β‐adrenergic receptors in adipocytes from parametrial, epididymal and inguinal fat depots.
A Fall in Blood Glucose Level Precedes Meal Onset in Free‐Feeding Rats
Authors: LOUIS‐SYLVESTRE J. , MAGNEN J. LE
Published: September 2012

LOUIS‐SYLVESTRE, J. AND J. LE MAGNEN. Chez les rats se nourrissant librement, une chute de glycémie précède chaque repas. NEUROSCI. BIOBEHAV. REV. Suppl. 1, 13–15, 1980 ‐ L'hypothèse selon laquelle la stimulation à manger ou éveil spécifique de faim a pur origine une chute de glucèmie induite par le déficit périodique entre production hépatique et utilisation périphérique du glucose est ancienne. Cependant, jusqu'a present, les résultats de déterminations épisodiques de la glycémie, pratiquées au cours des intervalles interprandiaux, chez le rat se nourrissant ad libitum n'ont pas apporte de preuve directe. Une technique permettant une détermination continue, de longue durée, de la glycémie chez le rat se nourrissant librement a été mise au point. Son utilisation a permis de montrer que 5 à 6 minutes avant tout repas, diurne ou nocturne, se produit une chute de glycémie de 6 à 8%.
Body Composition and Tissue Distributions in Growth Hormone Deficient Adults Before and After Growth Hormone Treatment
Authors: Lönn Lars , Johansson Gudmundur , Sjöström Lars , Kvist Henry , Odén Anders , Bengtsson Bengt‐Åke
Published: September 2012

This study examines short and long‐term effects of recombinant human growth hormone (rhGH) on body composition and regional tissue distributions by using a multicompartment technique based on computed tomography. Part I includes nine subjects aged 46 ± 9 years with adult onset GH deficiency who were examined before and in the end of 6 months treatment with rhGH (0.4 U. kg−1. week−1) in a double‐blind crossover trial. Part II is an ongoing open trial including seven of the males in part I. They were treated with rhGH (0.25 U. kg−1. week−1) over an additional period of 24 months.

Adipose tissue (AT) was reduced by 4.7 kg (p<0.01) while the muscle plus skin compartment (M) and visceral organs (V) were increased by 2.4 (p<0.05) and 0.7 kg (p<0.01), respectively, over 6 months of treatment with a high rhGH dose. A preferential lipid mobilization occurred in the visceral and subcutaneous trunk depots resulting in a changed AT distribution. Muscles of legs and arms increased while the increase of trunk muscles did not reach significance.

The body composition changes were maintained over 2 years additional treatment. The preferential loss in visceral AT was further pronounced while other changes in tissue distributions observed during the first 6 months tended to be reversed on the lower rhGH dosage.

It is concluded that growth hormone has profound and discordant effects on AT, M and V and with associated changes in tissue distributions. The beneficial effects on body composition seen in short‐term treatment is preserved throughout an additional 24 months period of treatment.
Fat Accretion and Growth in the Rat
Authors: ZUCKER THEODORE F. , ZUCKER LOIS M.
Published: September 2012

The normal course of fat accretion in male rats from birth to 3 years is described. The relative amount of fat and relative size of fat pads increased steadily throughout life (except for a brief cessation in fat accretion at weaning), in a manner closely related to body weight and independent of age. Several new rat strains with extremes of growth or fat accretion, fed the same diet, were used to define and illustrate courses of fat accretion: very large and very small non‐obese strains and a hereditarily obese rat. Rats of different known strains fed a variety of more refined diets show a course of fat growth different from that obtained with stock diets. Several types of obesity are discussed: insulin obesity, nutritional obesity, and hereditary obesity. Hereditary size and growth of the rat were readily (in a few generations) altered up or down, by consistently using the largest or the smallest 25% of the population for breeders. It is probable that the large increase in size of some laboratory rats over the past 40 years has been accomplished not only by improvement in stock diets and colony conditions, but also by selection for increased hereditary size.
Abnormal Regulation of Hepatic Glucocorticoid Receptor mRNA and Receptor Protein Distribution in the Obese Zucker Rat
Authors: Jenson Michelle , Kilroy Gail , York David A. , Braymer Douglas
Published: September 2012

This study examines the cellular distribution of glucocorticoid receptor (GR) protein and transcriptional activity of the GR gene in the liver of Zucker obese (fa/fa) rats. Immunoabsorption and Western blotting showed an increase in nuclear GR protein level but a decrease in cytosolic GR levels in the liver of 5‐week old male obese rats (fa/fa) compared to their lean littermates (Fa/‐). These changes were confirmed by receptor‐ligand binding assays with [3H]‐dexamethasone which showed a sixfold increase in average obese nuclear GR binding and a twofold reduction in cytosolic GR binding. HSP90, but not HSP70, levels were reduced in hepatic cytosol and increased in hepatic nuclei prepared from obese rats. Using Northern blot analysis of hepatic RNA, we demonstrated a twofold increase in hepatic mRNAs for GR, malic enzyme (ME), tyrosine aminotransferase (TAT), and glyceraldehyde 3‐P04‐dehydroge‐nase in the obese rat. Increased transcription of GR and ME mRNAs in obese nuclei was indicated in nuclear run‐on assays. These data suggest that there is increased nuclear localization of GR in the liver of obese rats and suggests that increased transcription of the GR gene may contribute to this effect. The described changes may contribute to the abnormal regulation by glucocorticoids of some hepatic genes in the Zucker fa/fa rat.
Ontogeny of the Response to Thyroxine (T4) in the Porcine Fetus: Interrelationships Between Serum T4, Serum Insulin‐Like Growth Factor‐1 (IGF‐1) and Differentiation of Skin and Several Adipose Tissues
Authors: Hausman Gary J. , Wright J. Thomas
Published: September 2012

The temporal aspect of thyroxine (T4) enhanced development of several fetal adipose tissue depots (locations) and skin was examined in the present study. On day 70 of gestation pig fetuses were either hypophysectomized (hypox), hypoxed and implanted with T4 pellets or left intact (control). Subsequently, fetuses were removed for study at either 73, 75, 80, 85 and 90 days of gestation. Serum levels of T4 and insulin‐like growth factor I (IGF‐I) were significantly elevated by T4 after 3 days of treatment and throughout the study. T4 treatment enhanced development of skin, inner and outer subcutaneous (SQ) adipose tissue and adipocyte lobules around hair follicles (HFL's) but degree of response and response time were tissue or depot dependent. The T4 response time was shortest for skin and HFL's, longest for inner SQ and intermediate for the outer SQ. Considering the entire treatment period, magnitude of the T4 response was much greater for skin and HFL's than for outer and inner SQ tissues.

Possibly, these developmental characteristics indicate that T4 directly influences skin and HFL's and indirectly influences inner SQ adipose tissue by increasing production of a locally produced adipogenic growth factor. Furthermore, developmental characteristics (morphological) indicated that putative local growth factor mediation of T4 action may depend on stage of development or maturity of the tissue. IGF‐I is clearly the most logical candidate as a putative local mediator of T4, but evidence at the molecular level is needed to prove this suggestion. Regardless, the particular adipose tissue location or depot is an important aspect of hormone responsiveness during the critical or sensitive period of fetal adipose tissue development.