bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a Fat Substitute, Sucrose Polyester, on Food Intake, Body Composition, and Serum Factors in Lean and Obese Zucker Rats
Authors: Grossman Barbara Mullen , Akoh Casimir C. , Hobbs Jerri K. , Martin Roy J.
Published: September 2012

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight‐week‐old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one‐half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control‐fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O‐FS) gained less weight as compared to obese control‐fed animals (O‐C). Lean rats given fat substitute (L‐FS) did not have significantly different body weights as compared to the L‐C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O‐FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O‐C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.
The Quantitative Relationship Between “The Metabolic Syndrome” and Abdominal Obesity in Women
Authors: Lapidus Leif , Bengtsson Calle , Björntorp Per
Published: September 2012

Abdominal obesity is closely associated with the presence of metabolic risk factors and elevated blood pressure in selected materials. This has, however, never been analyzed quantitatively in a non‐selected cohort. Therefore, in a population‐based study of 1462 Swedish women, four selected risk factors for non‐insulin dependent diabetes mellitus (NIDDM) and cardiovascular disease (CVD), serum triglycerides, blood glucose and systolic blood pressure and also serum insulin in a subsample, were examined in relation to regional and overall obesity. This was performed by subdividing the age adjusted sample into quintiles of waist to hip circumference ratio (WHR) or body mass index (BMI) as indicators of abdominal distribution of body fat and overall obesity, respectively. The risk factors serum triglycerides, blood glucose, blood pressure and serum insulin were defined as being elevated when the value of the risk factor was higher than the mean plus one or two standard deviations of the total age‐adjusted cohort. The percentage of women with elevated risk factors according to this definition was then calculated in each of these quintiles.

Having a risk factor which was elevated according to the definition was significantly correlated to WHR and BMI (p<0.0001) independent of age. The presence of one or several of these elevated risk factors was clearly higher than expected in the fifth quintile of WHR, and to a lesser extent in the fifth quintile of BMI while this was not the case in the lower quintiles of WHR and BMI. When studying the combination of the WHR and BMI, the presence of risk factors higher than the mean plus two standard deviations increased gradually with WHR in all five quintiles of BMI. A significant association was observed between WHR and presence of risk factors independent of BMI (p<0.0001) but BMI did not remain significantly correlated to presence of risk factors when controlling for WHR (p=0.09). These results indicate that abdominal distribution of body fat in women independently of general obesity is closely associated with metabolic risk factors including elevated blood pressure, a metabolic syndrome with increased risk for cardiovascular disease and non‐insulin dependent diabetes mellitus.
The Response to Exercise with Constant Energy Intake in Identical Twins
Authors: Bouchard Claude , Tremblay Angelo , Després Jean‐Pierre , Thériault Germain , Nadeauf André , Lupien Paul J. , Moorjani Sital , Prudhomme Denis , Fournier Guy
Published: September 2012

Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 ± 9.8 MJ (Mean ± SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p <0.001) and it was entirely accounted for by the loss of fat mass (p <0.001). Fat‐free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p <0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomography (CT). The reduction in CT‐assessed abdominal visceral fat was quite striking, from 81 cm2 (SEM = 5) to 52 cm2 (SEM = 6) (p <0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p <0.05). Intrapair resemblance was observed for the changes in body weight (p <0.05), fat mass (P <0.01), percent fat (p <0.01), body energy content (p <0.01), sum of 10 skinfolds (p <0.01), abdominal visceral fat (p <0.01), fasting plasma triglycerides (p <0.05) and cholesterol (p <0.05), maximal oxygen uptake (p <0.05), and respiratory exchange ratio during submaximal work (p <0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during sub‐maximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.
Comparison of the Lipolytic Effects of Norepinephrine and BRL 37344 in Rat Brown and White Adipocytes
Authors: Simard Pierre‐Michel , Atgié Claude , Mauriège Pascale , D'Allaire François , Bukowiecki Ludwik J.
Published: September 2012

The lipolytic effects of norepinephrine (a non‐selective β‐agonist) and BRL 37344 (a selective β3‐agonist) were compared in isolated rat brown and white adipocytes. Norepinephrine and BRL 37344 maximally stimulated lipolysis in brown and white adipocytes, approximately 10 times above basal values. However, adipocyte sensitivity for BRL 37344 was greater than that for norepinephrine, particularly in brown adipocytes [the EC50 values (nM) for BRL 37344 and norepinephrine were 5 ± 1 and 103 ± 31 in brown adipocytes (P <0.01) versus 56 ± 9 and 124 ± 17 in white adipocytes (P <0.05), respectively]. On the other hand, the lipolytic effects of norepinephrine were totally blocked by 20–40 times superior concentrations of propranolol or bupranolol in brown as well as in white adipocytes. In contrast, the lipolytic effects of BRL 37344 were fully inhibited by concentrations of propranolol or bupranolol that were 200–1000 superior to the β3 agonist concentration. The results demonstrate that: (1) the (β3‐agonist BRL 37344 is as effective as norepinephrine for maximally stimulating lipolysis in rat brown and white adipocytes, (2) both adipocyte types are more sensitive to the lipolytic effects of BRL 37344 than to those of norepinephrine, (3) although bupranolol is a better antagonist than propranolol on BRL 37344‐stimulated lipolysis, it cannot be considered as a specific β3‐antagonist, (4) brown adipocytes are 10 times more sensitive than white adipocytes to the lipolytic effects of BRL 37344, suggesting an important role of β3‐receptors in brown adipose tissue.
Associations of Body Mass and Body Fat Distribution with Parity Among African‐American and Caucasian Women: The CARDIA Study
Authors: Lewis Cora E. , Smith Delia E. , Caveny Jennifer L. , Perkins Laura L. , Burke Gregory L. , Bild Diane E.
Published: September 2012

Associations of parity with body fat and its distribution are poorly understood; therefore, we examined the relationships between parity and obesity in young adult women. Body mass index (BMI), skin folds, and waist‐hip ratio were compared in 1452 African‐American and 1268 Caucasian nonpregnant women aged 18 to 30, adjusting for age (where no age‐parity interactions were present), education, physical activity (assessed by questionnaire) and fitness (assessed by graded exercise test), dietary fat intake, alcohol and smoking. Adjusted mean BMI was significantly higher in African‐American women aged 25–30 years with three or more children (28.5 kg/m2) than in those with two (27.0 kg/m2), one (26.2 kg/m2), or no children (26.3 kg/m2). Similar trends were found in Caucasians (BMI = 23.3, 23.4, 23.7, 25.0 kg/m2 for parity = 0,1, 2, ≥ 3, respectively), but the mean BMI was significantly higher in African Americans in each parity group. The association between BMI and parity was not present among women 18–24 years of age. Skinfolds were directly associated with parity in African Americans only. Waist‐hip ratios were generally lower among nulliparous than parous women in both ethnic groups; race differences were present only among nulliparas. In conclusion, parity was associated with BMI in women aged 25 to 30 years but did not explain ethnicity‐related differences in body mass.
Extracellular Hypothalamic Monoamines Measured by In Vivo Microdialysis in a Rat Model of Dietary Fat‐Induced Obesity
Authors: Shimizu Hiroyuki , Fisler Janis S. , Bray George A.
Published: September 2012

We tested two hypotheses about monoamine neurotransmitters in two strains of rats that differ in their sensitivity to obesity when eating a high‐fat diet; 1) that the concentrations of norepinephrine and serotonin and of their metabolites differ in the extracellular fluid of tlie ventromedial hypothalamus of conscious, unrestrained Osborne‐Mendel and S 5B/PI rats, and 2) that these monoamines are altered differently between strains by a high‐fat diet. The monoamines were measured by HPLC in dialysate collected by in vivo microdialysis in rats eating a semisyntlietic low‐fat diet (10% of kcal as fat) and again after either two or seven days of eating a high‐fat diet (56 % of kcal as fat). Norepinephrine, serotonin (5‐HT), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) were lower in Osborne‐Mendel rats than in S 5BR1 rats eating the low‐fat diet. Norepinephrine and serotonin both increased in Osborne‐Mendel rats with the onset of tlie high‐fat diet so that Osborne‐Mendel and S 5B/PI rats no longer differed in these neurotransmitters. By day 7 of high‐fat feeding, the concentrations of 3‐methoxy‐4‐hydroxyplienylglycol (MHPG), 5‐HIAA and the 5‐HIAA/5‐HT ratio rose in both strains. Ambient extracellular monoamines in the medial hypothalamus are lower in Osborne‐Mendel rats than in S 5B/PI rats and the response of these catecholamines to dietary fat was greater in Osborne‐Mendel rats than in S 5B/PI rats.
No Specific Effect of Fluoxetine Treatment on Fasting Glucose, Insulin, Lipid Levels, and Blood Pressure in Healthy Men with Abdominal Obesity
Authors: Visser Maijolein , Seidell Jacob C. , Koppeschaar Hans P.F. , Smits Philip
Published: September 2012

In this paper we investigated the effect of fluoxetine (60 mg/d) on serum lipids, glucose and insulin concentrations and blood pressure by means of a randomized, double‐blind placebo controlled trial. Thirty‐eight overweight BMI: 26–30 kg/m2), nondiabetic, nonhypertensive men with an abdominal fat distribution (waist/hip ratio: >0.97) received dietary advice and placebo or fluoxetine for 12 weeks.

The changes in serum parameters and blood pressure in the fluoxetine treated group were not different from the placebo treated group, despite a significantly larger weight loss in the fluoxetine group. In both groups serum total‐cholesterol concentrations, serum LDL‐cholesterol concentrations and tlie HDL/LDL ratio were significantly improved after treatment. Reductions in fasting glucose concentration and systolic blood pressure were only significant in the placebo group. A reduction of serum triglycerides and an increase of HDL‐cholesterol were found in the fluoxetine treated group.

In the total study population the changes in serum lipids seemed to be more strongly related to the change in total body fat or subcutaneous abdominal fat (assessed by MRI) compared to the change in visceral fat. The improvement of most of the serum lipids was related to tlie change in total body fat independent of the mechanism for attaining this fat loss.

Our results indicate that fluoxetine treatment has no specific effect beyond that expected for weight loss on serum lipid, glucose and insulin concentrations, and blood pressure in overweight men.
Skeletal Muscle Metabolism and Body Fat Content in Men and Women
Authors: Jean‐Aimé  , Dr. Simoneau  , Bouchard Claude
Published: September 2012

The purpose of the present study was to verify the relationships between indicators of body Eat content and specific characteristics of skeletal muscle in a large sample of men and women. Six skinfold thicknesses (σ6S) and maximal oxygen uptake (VO2 max) were measured in 348 Caucasian subjects (149 women and 199 men). Fiber type proportions (type I, type IIA, and type IIB) and activity levels of marker enzymes for the Krebs cycle (malate dehydrogenase, MDH) and for the fatty acid oxidation (3‐hydroxya‐cyl CoA dehydrogenase, HADH) pathways were determined in vastus lateralis muscle samples. No significant correlation was found between fiber type proportions and σ6S. Significant and negative correlations were, however, obtained in both genders between the σ6S and MDH enzyme activity (r = −0.23; p<0.01), but not between the σ6S and HADH enzyme activity. When individuals with low and high amount of subcutaneous fat but paired for VO2max were compared, vastus lateralis of fat men exhibited the same proportion of type I fiber (38.6 ± 10.3 vs 38.5 ± 13.4 %) and HADH activity level (3.43 ± 1.05 vs. 334 ± 0.81 U/g), but had about 20% less MDH enzyme activity than vastus lateralis of leaner men (158 ± 35 vs. 198 ± 43 U/g;p<0.05). No difference was found in any of these muscle phenotypes when comparisons were made between women with low and high amount of subcutaneous fat but also paired for VO2max. Moreover, no relations were observed between skeletal muscle fiber type proportion or metabolic markers with relative subcutaneous fat distribution. In conclusion, these results indicate that the proportion of fiber type of skeletal muscle is not a determinant of body fat content or fat distribution in men and women. However, the results of the present study suggest, at least in men, that a low oxidative capacity of skeletal muscle, undetected by muscle fiber typing, is associated with an augmented body fat content.
Long‐Term Weight Cycling in Female Wistar Rats: Effects on Metabolism
Authors: Lu Huiqing , Buiso Anne , Uhley Virginia , Jen K‐L Catherine
Published: September 2012

LU, HUIQING, ANNE BUISON, VIRGINIA UHLEY AND K‐L CATHERINE JEN. Long‐term weight cycling in female Wistar rats: effects on metabolism. Obes Res.

Weight cycling (WC) induced by ad‐lib and restricted high fat (HF) feeding has been shown to reduce final body weight but not body fat percent in female Wistar rats. We examined the metabolic consequences of this type of WC. Five groups of female Wistar rats were fed a HF diet and the sixth group was fed a low fat diet to serve as a control group. Of the five HF groups, four groups were weight cycled by ad‐lib and restricted feeding of the HF diet One of these groups weight cycled three times (HFCYC group) while the remaining three groups weight cycled once only, corresponding to the first, second and the third cycle of the HFCYC group. HF feeding induced hyperinsulinemia, hypertriglyceridemia, insulin resistance and elevated adipose tissue lipoprotein lipase (AT‐LPL) activity levels as compared to rats fed the low fat (LF) control diet. WC further increased blood insulin concentrations and insulin resistance in rats with three cycles of WC. However, blood pressure was not affected by HF feeding or WC. The magnitude of increase of AT‐LPL was reduced in weight cycled, HF fed obese rats after 15 weeks refeeding. We concluded that even though WC did not enhance weight gain nor impair weight loss, it did facilitate the development of insulin resistance and may predispose animals to diabetes.
Sertraline and Relapse Prevention Training Following Treatment by Very‐Low‐Calorie Diet: A Controlled Clinical Trial
Authors: Wadden Thomas A. , Bartlett Susan J. , Foster Gary D. , Greenstein Robert A. , Wingate Barbara J. , Stunkard Albert J. , Letizia Kathleen A.
Published: September 2012

WADDEN, THOMAS A, SUSAN J BARTLETT, GARY D FOSTER, ROBERT A GREENSTEIN, BARBARA J WINGATE, ALBERT J STUNKARD AND KATHLEEN A LETIZIA. Sertraline and relapse prevention training following treatment by very‐low‐calorie diet: a controlled clinical trial.Obes Res.

This study examined the combination of sertraline, a selective serotonin reuptake inhibitor, and relapse prevention training in the maintenance of weight loss following treatment by a very‐low‐calorie diet. A total of 53 women who had lost a mean (± SD) of 22.9 ± 7.1 kg from a pretreatment weight of 103.1 ± 17.8 kg were randomly assigned to a 54‐week weight maintenance program that was combined with either: 1) 200 mg/d of sertraline; or 2) placebo. During the first 6 weeks, sertraline subjects lost significantly more weight and reported significantly greater reductions in hunger and preoccupation with food than did subjects on placebo. After this time, however, women in both conditions regained weight steadily. The 13 sertraline subjects who completed the 54‐week study regained 17.7 ± 10.6 kg of their original 26.3 ± 7.6 kg loss, equal to a regain of 70.9 ± 41.7%. The 17 placebo completers regained 11.8 ± 9.0 kg of their 23.4 ± 7.8 kg loss, equal to a 46.5 ± 34.6% regain. End‐of‐treatment differences between groups in weight change were not statistically significant. Nor were there significant differences between the two conditions at any time in changes in fat‐free mass, resting metabolic rate or dysphoria, all of which tended to increase with weight regain. The results are discussed in relation to findings from other long‐term studies that combined diet and medication.
Clinical Studies with Mazindol
Authors: Inoue Shuji
Published: September 2012

An anoerxiant, mazindol suppresses food intake by 1)stimulating β‐adrenergic receptors, 2)inhibiting the feeding center and, 3)stimulating the satiety center in the hypothalamus. In Japan, mazindol is available for clinical use. We examined the effects of mazindol on 1) body weight, appetite, and abnormalities of obesity‐related diseases in long‐term use 2)maintenance of the reduced body weight after very‐low‐calorie diet (VLCD) therapy 3)combined use with VLCD therapy and, 4)inhibition of body weight gain in Prader‐Willi syndrome. In long‐term effects of mazindol, the average reduction of individual body weight was around 6.8 kg. The appetite of 59% of obese subjects was moderately suppressed. Systolic blood pressure, serum GOT, serum triglyceride, serum cholesterol, and glucose tolerance were also improved. With mazindol, 53.3% of obese subjects kept the reduced body weight after VLCD, in contrast, 20.0% of them kept it without mazindol. Combined use of mazindol with VLCD made the VLCD therapy more effective in out patients. Two of 3 patients with Prader‐Willi syndrome inhibited their body weight gain with mazindol. Thus, mazindol produced positive effects in these studies, although the effects were limited.
Obesity in Europe
Authors: Seidell Jacob C.
Published: September 2012

Obesity, defined as a body mass index > 30 kg/m2 is relatively common in Europe, particularly among women, and especially in Southern and Eastern European countries. Among men the distribution of body mass index values is surprisingly similar in most countries of Europe.

Educational level is strongly inversely associated with the prevalence of obesity. Although differences in body mass index cannot entirely explain the large variation in risk factors and mortality from coronary heart disease, it can be shown that within populations an increased body mass index is associated with less favorable risk patterns. More research is needed to elucidate the reasons for the large variation in the prevalence of obesity among European women and to the health risks associated with obesity in different European countries.
Growth and Body Mass Index of Brazilians Ages 9 Through 17 Years
Authors: Sichieri Rosely , Recine Elisabetta , Everhart James E.
Published: September 2012

Obesity during adolescence is considered a strong predictor of adult obesity, and obesity and overweight have been increasing among Brazilian adults. To gauge the relative frequency of overweight among adolescents in Brazil, we compared the distributions of body mass index (kg/m2) and stature in national population based samples of the U.S. and Brazil.

U.S. adolescents were on average about 10 cm taller than Brazilians, although growth spurts occurred at the same age for both populations. Brazilian adolescents were leaner than their U.S. counterparts. This difference was reduced among girls in the postpubertal period. At age 17 years, U.S. boys were about 10 kg heavier than Brazilian boys, but the difference among girls was only 2 kg. In families above the poverty level in the more developed South region, body mass index distribution for boys was closer to that of the U.S., and older girls tended to have higher body mass index than U.S. girls. Within Brazil, body mass index varied by ethnicity with Mulattos, but not Blacks, of both sexes having lower body mass index than Whites of the same age. Urban adolescents had higher body mass index than those living in rural areas. In general, the patterns seen among Brazilian adults were found among children. Among girls, in particular, overweight has become an identifiable problem during adolescence.
Abnormalities of Fuel Utilization as Predisposing to the Development of Obesity in Humans
Authors: Schutz Yves
Published: September 2012

A number of recent investigations in man have demonstrated that a low ratio of fat to carbohydrate oxidation (i.e., a high respiratory quotient or RQ) was associated with actual and/or subsequent body weight gain in obese non‐diabetic Pima Indians, in American men of various ages and in post‐obese European women investigated shortly after the cessation of a hypocaloric diet. It is well known that numerous exogenous and endogenous factors influence the RQ at rest such as: the level of feeding (positive vs. negative energy balance), the composition of food eaten (high vs. low carbohydrate), the size of the glycogen stores, the amount of adipose tissue as well as genetic factors. It should be stressed that some nutritional situations can coexist during which a low ratio of fat to carbohydrate is observed (i.e., a high RQ) despite weight loss. Furthermore, in most studies mentioned above, the low fat to carbohydrate oxidation ratio explains less then 10% of the variance in weight gain, suggesting that numerous additional factors also play a substantial role in the onset of weight gain.

It is concluded that: 1) A low fat to carbohydrate oxidation ratio or an abnormal fat oxidation is difficult to define quantitatively since it is largely influenced by the energy level and the composition of the diet. 2) Following a dynamic adaptation phase to positive energy balance, a low fat oxidation is progressively compensated: increased body fat is the price to pay for normalizing fat oxidation since, at least in resting conditions, there is an increase in fat oxidation of approximately 20 g/day for each 10 kg additional fat gain. The subject with a low fat to carbohydrate oxidation ratio will equilibrate at a body fat level allowing to reach a new fat balance.
Pathophysiology and Pathogenesis of Visceral Fat Obesity
Authors: Matsuzawa Yuji , Shimomura Iichiro , Nakamura Tadashi , Keno Yoshiaki , Kotani Kasuaki , Tokunaga Katsuto
Published: September 2012

Based on the analysis of fat distribution by computed tomography (CT) scans, the classification scheme for obesity should include visceral fat obesity in which fat accumulation is predominant in the intra‐abdominal cavity. Obese subjects with visceral fat accumulation more frequently demonstrate impairment of glucose and lipid metabolism than those with subcutaneous fat accumulation. We have shown that visceral fat obesity is present in almost 90% of obese patients with ischemic heart disease. Even in non‐obese subjects, visceral fat accumulation is correlated with glucose intolerance, hyperlipidemia and hypertension. Forty percent of non‐obese subjects with coronary artery disease (CAD) had increased visceral fat. In non‐obese subjects, visceral fat area assessed by abdominal CT at the level of the umbilicus correlates with metabolic risk factors, whereas in obese subjects the visceral fat area to subcutaneous fat area ratio provides a more significant correlation.

From clinical and basic investigations, aging, sex hormones, excess intake of sucrose and lack of physical exercise have been suggested to be determinants for visceral fat accumulation. Since intra‐abdominal fat (mesenteric and omentum fat) has been shown to have high activities of both lipogenesis and lipolysis, its accumulation can induce high levels of free fatty acids, a product of lipolysis, in portal circulation which go into the liver. Excess free fatty acids may cause the enhancement of lipid synthesis and gluconeo genesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis.

Thus we propose a disease entity, visceral fat syndrome, which may increase susceptibility to atherosclerosis due to multiple risk factors induced by visceral fat accumulation.
A Very‐Low‐Calorie Conventional Japanese Diet: Its Implications for Prevention of Obesity
Authors: Sakata Toshiie
Published: September 2012

A very‐low‐calorie conventional Japanese diet of 370 kcal/day has been shown to be useful for weight reduction and its long‐term maintenance. Sources of the diet were mainly from chicken fillet, egg white, fish white‐meat, mushroom, seaweed and low‐or non‐calorie fiber‐rich vegetable, and contained 4.4g fat, 38.1g protein, 45.2g carbohydrate and essential minerals and vitamins. However, metabolic and neural implications of a commercial very‐low‐calorie liquid formula diet have rarely been investigated from the view point of food intake and appetite regulation. Animal studies have demonstrated the rationale for efficacy of the very‐low calorie conventional Japanese diet as follows: (1)Increased hypothalamic histamine suppressed food intake through H1‐receptors in the ventromedial hypothalamus (VMH) and paraventricular nucleus, the satiety centers. (2) Low energy intake enhanced satiety and decreased food intake through histaminergic activation of VMH neurons. (3) Mastication activated afferent signal transmission from proprioceptors in the oral cavity to the mesencephalic trigeminal nucleus(Me5). Histaminergic systems in the hypothalamus were activated by mastication and low energy supply, which was accompanied by satiation through the action of histamine in the VMH. Usefulness of the very‐low‐calorie conventional Japanese diet derives from utilization of conventional Japanese food stuffs as a fiber rich, low energy food source, and from enhancement of satiation by increased mastication required of the diet. The properties of the diet seemed to effect a closed positive feedback loop between histaminergic activation in hypothalamic satiety centers and behavioral changes to enhance satiation and cause feeding suppression.
Antiaging Action of Caloric Restriction: Endocrine and Metabolic Aspects
Authors: Masoro Edward J.
Published: September 2012

Restricting the energy intake of mice and rats slows the rate of actuarial aging, delays or prevents most age‐associated disease processes, and maintains physiological processes in a youthful state at advanced ages. This manipulation is effective when initiated in young animals or in adult life. Although body fat is decreased by this reduction in energy intake, the reduction in body fat is not causally related to the antiaging action. Nor does this reduction in energy intake slow the aging processes by decreasing the metabolic rate, but it may do so by altering the characteristics of fuel use. Another possible mechanism underlying the antiaging action is the general protection restriction of energy intake provides against harmful agents, an action which may be the result of an alteration in adrenal glucocorticoid physiology.
Who Are the Weight Maintainors?
Authors: Jeor Sachiko T. St. , Brunner Robert L. , Harrington Melanie E. , Scott Barbara J. , Cutter Gary R. , Brownell Kelly D. , Dyer Alan R. , Foreyt John P.
Published: September 2012

To characterize people who maintain weight over long periods of time, normal weight and obese adults (n=385) were studied over five annual visits. Subjects were classified using a ± 5 lb change between the first and the fifth year visits to determine overall maintenance (M), with gain (G) or loss (L) being any change outside this range. This MGL status was cross‐tabulated with a Fluctuation Index which counted the number of successive year‐to‐year weight changes of more than ± 5 lbs (F0 through F4). True maintainers were defined as those having all weight changes within ± 5 lbs during the 5‐year period (M and F0).

Nineteen percent (n=73) of the subjects were classified as True Maintainers and included three times as many normal weight as obese subjects. Obese subjects comprised only 25% of the True Maintainer group but 60% of the Non‐Maintainer group. Age had no association with Maintainer status. Standard measures of weight variability were lowest among True Maintainers and highest in Non‐Maintainers. In addition, True Maintainers had lower BMI, Percent Body Fat, and Waist‐Hip Ratios than Non‐Maintainers. Subjects classified as Non‐Maintainers were more likely to engage in dieting, by a variety of measures, than True Maintainers—this was particularly true among obese subjects. Finally, changes in total cholesterol, LDL and HDL cholesterol, and systolic and diastolic blood pressure were not reliably associated with Maintainer status, although the ordering of the group means suggested that True Maintainers had slightly healthier levels of “risk” variables. Overall, the results suggest that True Maintainers comprise a potentially important and interesting group of individuals who need further study.
Visceral Fat Accumulation and Cardiovascular Disease
Authors: Matsuzawa Yuji , Nakamura Tadashi , Shimomura Iichiro , Kotani Kazuaki
Published: September 2012

Classification of Obesity. It has been noted that the incidence of metabolic complications among equally obese subjects differs depending on their physique (11) and there has been more scientific assessment in recent years that complications such as diabetes mellitus or hyperlipidemia are related to adipose tissue distribution (5). In 1983, we reported a method for adipose tissue analysis using computed tomography (CT), which enables the analysis of adipose tissue in the body cavity, e.g., abdominal cavity or thoracic cavity, as well as subcutaneous fat (10). Using this method, we found that the patients with accumulation of fat in the abdominal cavity have a higher incidence of complication (1).

Based on this finding, we proposed a classification into visceral fat obesity by visceral fat area (V)/subcutaneous fat area (S) ratios obtained from CT cross sectional pictures of the umbilical region. We divided obese subjects at a V/S ratio of 0.4, classifying those with a ratio of 0.4 or more as a visceral fat obesity group and those with V/S ratio of below 0.4 as a subcutaneous fat obesity group. Disorders of glucose and lipid metabolism were more marked in the visceral fat obesity than subcutaneous fat obesity even when sex and age were matched. We also demonstrated that visceral fat obesity is more frequently accompanied by circulatory disorders such as left ventricular enlargement (8) and hypertension than subcutaneous fat obesity (2).
The Addition of Dexfenfluramine to Fluoxetine in the Treatment of Obesity: A Randomized Clinical Trial
Authors: Pedrinola Filippo , Sztejnsznajd Cláudia , Lima Nicolau , Halpern Alfredo , Medeiros‐Neto Geraldo
Published: September 2012

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short‐term weight‐loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty‐three patients were randomly assigned in a double‐blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n=13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n=20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean ± SEM 6.2 ± 2.8 kg and Group II 13.4 ± 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m2. However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL‐cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.
Reduction of Visceral Adipose Tissue and Improvement of Metabolic Indices: Effect of Dexfenfluramine in NIDDM
Authors: Marks Sharon J. , Moore Niall R. , Clark Mo L. , Strauss Boyd JG , Hockaday T. Derek R.
Published: September 2012

Increased visceral adipose tissue is thought to contribute to impaired glucose tolerance. We studied 10 men with non‐insulin dependent diabetes (NIDDM) before and after a 12‐week intervention study using dexfenfluramine. Subjects had a mean body mass index (BMI) of 26.4 ± 1.7 kg\m2 and had an abdominal distribution of body fatness (waist‐to hip ratio >0.9). Anthropometric indices, biochemistry, macronutrient intake from 7‐day food records as well as a euglycaemic glucose clamp and magnetic resonance imaging (MRI) were performed at week 0 and week 12. Abdominal adipose tissue area measured by MRI was reduced from 854 ± 270 cm2 to 666 ± 231 cm2 (p=0.003) due mainly to a selective 32% reduction in visceral fat area from 484 ± 230 cm2 to 333 ± 72 cm2 (p=0.002). Insulin sensitivity improved from 0.29 ± 0.13 [min−1 (mU/L)] to 0.54 ± 0.21 [min−1 (mU/L)] (p=0.01) and C‐peptide levels reduced from 0.77 ± 0.24 μmol/L to 0.58 ± 0.15 μmol/L (p=0.002). The reductions in fasting glucose and glycated haemoglobin failed to achieve significance. Fasting total cholesterol and triglyceride levels significantly reduced (p=<0.001 and p=0.021 respectively). There was a reduction in total energy intake (p=0.005) due to a significant reduction in calories obtained from fat (p<0.001). Thus dexfenfluramine was shown to be a useful adjunct therapy for the reduction of visceral fat in abdominally‐obese men with NIDDM with an associated improvement in insulin sensitivity.
The 3‐Phosphorylated Phosphoinositide Response of 3T3‐L1 Preadipose Cells Exposed to Insulin, Insulin‐Like Growth Factor‐1, or Platelet‐Derived Growth Factor
Authors: Sorisky Alexander , Pardasani Dheerja , Lin Ying
Published: September 2012

We compared the pattern of 3‐phosphorylated phosphoinositides produced by confluent 3T3‐L1 preadipose cells upon exposure to growth factors that either induce differentiation (insulin, insulin‐like growth factor‐1) or do not (platelet‐derived growth factor). Following addition of insulin or insulin‐like growth factor‐1, PI(3,4,5)P3 rapidly rose, on average, to levels tenfold over basal. PI(3,4)P2 either did not change (after insulin) or slightly increased (1.5 fold). Time course studies with insulin demonstrated that the rise in PI(3,4,5)P3 peaked by 1 minute, and levels then remained steady over 30 minutes. Dose‐response experiments showed that insulin at a concentration of 1 nM was sufficient for the PI(3,4,5)P3 response. Insulin failed to increase PI(3,4)P2 at any of the time points or at any of the doses used. In contrast, after addition of platelet‐derived growth factor, both PI(3,4)P2 and PI(3,4,5)P3 rose concurrently and to comparable extents. These data suggest that one possible mechanism contributing to insulin/insulin‐like growth factor‐1‐induced 3T3‐L1 preadipose cell differentiation is a distinct pattern of 3‐phosphorylated phosphoinositide accumulation, defined by a prominent increase in PI(3,4,5)P3 with no (in the case of insulin), or a minimal (in the case of IGF‐1), rise in PI(3,4)P2.
Autonomic Activity Assessed by Heart Rate Spectral Analysis Varies with Fat Distribution in Obese Women
Authors: Gao Young Y. , Lovejoy Jennifer C. , Sparti Andrea , Bray George A. , Keys L. Ken , Partington Curtis
Published: September 2012

Obesity in humans has been associated with altered autonomic nervous system activity. The objective of this study was to examine the relationship between autonomic function and body fat distribution in 16 obese, postmenopausal women using power spectrum analysis of heart rate variability. Using this technique, a low frequency peak (0.04‐0.12 Hz) reflecting mixed sympathetic and parasympathetic activity, and a high frequency peak (0.22‐0.28 Hz) reflecting parasympathetic activity, were identified from 5‐minute consecutive heart rate data (both supine and standing). Autonomic activity in upper body (UBO) vs. lower body obesity (LBO)(by waist‐to‐hip ratio) and subcutaneous vs. visceral obesity (by CT scan) was evaluated. Power spectrum data were log transformed to normalize the data. The results showed that standing, low‐frequency power (reflecting sympathetic activity) and supine, high‐frequency power (reflecting parasympathetic activity) were significantly greater in UBO than in LBO, and in visceral compared to subcutaneous obesity. Women with combined UBO and visceral obesity had significantly higher cardiac sympathetic and parasympathetic activity than any other subgroup. We conclude that cardiac autonomic function as assessed by heart rate spectral analysis varies in women depending on their regional body fat distribution.
Genetic Pleiotropy for Resting Metabolic Rate with Fat‐Free Mass and Fat Mass: The Québec Family Study
Authors: Rice Treva , Tremblay Angelo , Dériaz Olivier , Pérusse Louis , Rao DC , Bouchard Claude
Published: September 2012

Shared genetic and familial environmental causes for the associations among resting metabolic rate (RMR), fat‐free mass (FFM), and fat mass (FM) were investigated in families participating in phase 2 of the Québec Family Study. A multivariate familial correlation model assessing the pattern of significant cross‐trait correlations between family members (e.g., RMR in parents with FFM in offspring) was used to infer the etiology of the associations. For each of FM and FFM with RMR, significant sibling, parent‐offspring, and intraindividual cross‐trait correlations suggest the associations are familial. Furthermore, the lack of significant spouse cross‐trait correlations suggests that the familial aggregation is primarily genetic. Bivariate heritability estimates suggest that as much as 45% to 50% of the shared variance between FFM and RMR may be genetic, and as much as 28% to 34% for FM and RMR. This study supports the notion that the gene(s) affecting each of FFM and FM also influence the RMR. Moreover, the lack of any familial associations between FFM and FM suggests that the effects of each body size component on RMR are independent, i.e., more than one genetic source on the RMR‐body size association. The possibility that RMR is an oligogenic trait (i.e., more than one underlying genetic etiology) should be further investigated using more complex multivariate segregation methods until specific genes can be tested.
Mental Distress, Obesity and Body Fat Distribution in Middle‐Aged Men
Authors: Rosmond Roland , Lapidus Leif , Mårin Per , Björntorp Per
Published: September 2012

Previous epidemiological studies have suggested that psychiatric symptoms are associated with obesity and abdominal distribution of body fat in women. The aim of the present study was to examine this in middle‐aged men.

In 1992 a cluster selected cohort of 1040 men born in 1944 (participation rate 79.9%) was examined. Registrations of symptoms of depression and anxiety, sleep disturbances, psychosomatic disease as well as degree of life satisfaction were analyzed in relation to body mass index (BMI) and the waist/hip circumference ratio (WHR). In univariate analyses both BMI and WHR correlated with these factors. BMI and WHR were, however, closely interrelated (p=0.61), necessitating analyses of separate, independent relationships in multivariate analyses.

When adjusted for WHR all the significant relationships with BMI disappeared. In contrast the WHR, adjusted for BMI, showed remaining significant associations with the use of anxiolytics (p=0.018), hypnotics (p=0.029), antidepressive drugs (p=0.008), degree of melancholy (p=0.002), and life satisfaction (p=0.002, negative), difficulties to sleep (p=0.014) and fall asleep (p=0.047), tendency to wake up from sleep (borderline, p=0.070) and dyspepsia (p < 0.001).

Since smoking and alcohol are known to influence on the WHR, these factors were, in addition to BMI, entered into the analyses as confounding variables. The mentioned associations then remained statistical significant (use of hypnotics borderline, p=0.074) except difficulties to fall asleep and tendency to wake up.

It was concluded that in contrast to BMI, the WHR is associated with symptoms of depression and anxiety with associated sleep disturbances, as well as psychosomatic symptoms and dissatisfaction. It was hypothesized that the mechanism involved might be increased secretion of Cortisol, directing storage fat to central adipose tissue depots.
Inhibition of Cortisol Secretion by Dexamethasone in Relation to Body Fat Distribution: A Dose‐Response Study
Authors: Ljung Thomas , Andersson Björn , Bengtsson Bengt‐Åke , Björntorp Per , Mårin Per
Published: September 2012

In this study, dexamethasone (dex) was administered in random order in doses of 0.05, 0.125, 0.25 and 0.5 mg at 10 p.m. with measurements of serum Cortisol in the morning (8 a.m.) of this and the following day. The test was performed on 22 apparently healthy men, 40 to 60 years of age, recruited from laboratory personnel, outpatient clinics or advertisements in a newspaper. Eight had a body mass index (BMI) (kg/m2) of <25 and 14 of >25. Twelve men had a waist hip ratio (WHR) of <1.0 and 10 men had a WHR of<1.0.

Cortisol values at baseline were correlated inversely with WHR and were usually lower in men with a high (>1.0) rather than a low than low (<1.0) WHR after dex inhibition. There was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a WHR of >1.0. In addition, the inhibition at 0.5 mg dex correlated negatively with the WHR and was significantly lower (p<0.05) in men with a WHR of >1.0 than in men with a WHR of <1.0. None of these differences or relationships was found to be dependent on BMI.

It is concluded that men with an elevated WHR experience a decrease in the inhibition of Cortisol secretion by dex. It is suggested that this could explain or contribute to the elevated sensitivity of their HPA axis. Furthermore, lower morning Cortisol concentrations suggest a change in diurnal secretion patterns.
Obese (ob) Gene Defects are Rare in Human Obesity
Authors: Carlsson Björn , Lindell Kajsa , Gabrielsson Britt , Karlsson Cecilia , Bjarnason Ragnar , Westphal Otto , Karlsson Ulla , Sjöström Lars , Carlsson Lena M.S.
Published: September 2012

Our knowledge of the role of the recently cloned ob‐protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob‐gene expression, with extreme overexpression in mice which lack bioactive ob‐protein, have nonfunctional ob‐receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob‐gene expression was examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Northern blot. The coding region of the ob‐gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob‐gene and ob‐gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob‐expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob‐gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob‐gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
A Low Sympathoadrenal Activity is Associated with Body Weight Gain and Development of Central Adiposity in Pima Indian Men
Authors: Tataranni P. Antonio , Young James B. , Bogardus Clifton , Ravussin Eric
Published: September 2012

TATARANNI P ANTONIO JAMES B YOUNG, CLIFTON BOGARDUS, ERIC RAVUSSIN. A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men.

To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men (28 ± 6 years, 101 ± 25 kg, 34 ± 9% body fat, mean ± SD) in whom sympathoadrenal function was estimated at baseline by measurements of 24‐hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight‐maintenance conditions. Body weight, body composition (hydrodensitometry), and body fat distribution (waist‐to‐thigh circumference ratio, W/T) were measured at baseline and follow‐up. Follow‐up data were available on 44 subjects who gained on average 8.4 ± 9.5 kg over 3.3 ± 2.1 years. In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain (r=−0.38; p=0.009). Baseline Epi excretion rate correlated negatively with changes in W/T (r=−0.44; p=0.003). In conclusion, our data show for the first time that a low sympathetic nervous system activity is associated with body weight gain in humans. Also, a low activity of the adrenal medulla is associated with the development of central adiposity.