Dietary Fat Is Shunted Away from Oxidation,Toward Storage in Obese Zucker Rats

BESSESEN, DANIEL H, CONNIE L RUPP AND ROBERT H ECKEL. Dietary fat is shunted away from oxidation, toward storage in obese zucker rats. Obes Res. 1995;3:179–189. Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue (ATLPL) of lean and obese Zucker rats have consistently documented increased activity in obese rats relative to lean. Since LPL is considered to be rate limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and adipose tissue, these data have been used to suggest that the metabolic partitioning of TGFA favors storage over oxidation in obese rats. To document the partitioning of TGFA directly, the fate of ¹⁴C labeled oleic acid (42nmols) was fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to chronically reduce weight 25% below that of obese controls (reduced-obese). The amount of ¹⁴C recovered in CO₂ over 6 hours following ingestion was significantly less in obese rats compared to lean (0.45 ± 0.06 vs. 0.88 ± 0.09nmols, p=.0004) and less still in the reduced obese group (0.34 ± 0.06nmols p=.00003). Six hours after ingestion, the quantity of label found in adipose tissue was significantly greater in the obese rats compared to lean (14.51 ± 1.92 vs. 1.38 ± 0.29nmols p<.00001), but was intermediate in the reduced-obese group (9.23 ± 0.98nmols p=.0003). At 2.2 hours there was significantly more label in skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 ± 0.24; 1.35 ± 0.04nmols p=.01; 1.41 ± 0.27nm p=.02). However, at 6 hours these differences between groups were no longer present. These findings Indicate that dietary fat is shunted away from oxidation toward storage in obese Zucker rats. Additionally it appears that there may be a relative block in the oxidation of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative normalization of this partitioning defect in reduced-obese rats is at variance with what was suggested by previous measurements of tissue specific levels of LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to muscle in reduced-obese rats. This could occur through increased delivery of non-esterified fatty acids (NEFA) to muscle as a result of an increase in net lipolysis.     

Maintenance of Weight Loss: A Needs Assessment

This study identified facilitators and obstacles to maintenance of weight loss following a very-low-calorie-diet and behavior modification program. A survey was mailed to a random sample of 178 program completers and received a 61% response rate; the most frequent follow-up period was more than 2 years. Twenty-nine percent reported weighing the same (within 10 lbs) or less than the end of their participation in the treatment program (maintainers), while 71% reported their present weight was a mean of 65% higher than their initial weight loss (regainers). Maintainers were significantly more likely to report engaging in regular aerobic exercise, attending a maintenance support group, and confidence in their ability to manage their weight in the future, while regainers were more likely to report stress and motivation as frequent weight management obstacles. Respondents consistently identified the need for low/no cost ongoing support. Maintainers and relapsers reported similar challenges in managing their weight, yet with different results, suggesting the need to identify subgroups for which different post-treatment support options could be applied.     

Topical Fat Reduction

The fat on women's thighs is more difficult to mobilize due to increased α-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (β adrenergic) or inhibition (adenosine or α-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing wereperformed. Trial#5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.     

Drugs That Cause Weight Gain

Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent and problematic body weight gain in many treated patients. Major depressive illness is often associated with reductions in appetite and body weight, and treatment with antidepressants effectively restores mood, appetite and weight. However, a frequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, oftentimes resulting in medication noncompliance. The incidence of weight gain during acute and chronic treatment with different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain.     

Combined Drug Treatment of Obesity

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.     

Black and White Females' Perceptions of Ideal Body Size and Social Norms

Different cultural norms and standards for appropriate female body size might contribute to the disparity in obesity rates between black and white adult females (46.0% and 24.6% respectively). The purpose of this study was to measure adolescents' perceptions of ideal size and social norms regarding female body size as well as adolescents' perceptions of significant others' evaluation and expectations of the adolescents' body size. Subjects included 437 adolescent girls (247 white and 190 black) aged 13 to 19 (x=44.9, SD=.979) from six randomly selected public schools. The subjects, heights and weights were measured. Responses to a body image questionnaire and a series of nine female body drawings (arranged ordinally, 1 to 9, from thinnest to heaviest) were analyzed using the General Linear Model and Logistic Regression. The female body size considered ideal by black females was significantly larger than the size selected as ideal by white females (x= 3.47 and x= 3.13 respectively, p< 0.001). Black females were two times more likely than white females to describe themselves as thinner than other girls their age (O.R. = 2.01, 95% C.I.1.34, 3.01) and seven times as likely to say that they were not overweight (O.R. = 7.08, 95% C.I. 3.72, 13.45). White females wanted to be a smaller size than they currently were and felt encouraged by significant others to lose weight or reduce their size. Black females did not indicate as great a desire as whites to be smaller and they tended to feel that their size was considered satisfactory by significant others. Only subjects from the low SES group perceived that significant others wanted them to gain weight. The differences between black and white subjects' beliefs and perceptions about body size norms may explain, in part, why heavier body weights persist in some cultural groups.     

Growth Hormone Secretion after Testosterone Administration to Men with Visceral Obesity

Visceral obese men were characterized by a decreased total GH secretion and diminished peak amplitude, size, and number. T-substitution was followed by elevation of IGF-I levels. The IGF-I increase correlated with the elevation of T-concentration, and was most pronounced in men with the lowest concentrations of free T from the outset. There were no detectable changes in total quantity, amplitude, size or number of peaks of GH secretion. Glucose, cholesterol and triglycerides as well as diastolic blood pressure decreased. There were no changes in thyroid or hematology variables. Visceral obesity in men has been reported to be characterized by low testosterone (T) and insulin-like growth factor I (IGF-I) concentrations, the latter suggesting a relative growth hormone (GH) deficiency. Since T and GH-secretions are interrelated, men with visceral obesity were substituted with T for 14 days, and diurnal secretion pattern of GH as well as IGF-I concentrations, and metabolic variables were followed. T-substitution of visceral obese men is followed by an elevation of IGF-I concentrations. It is suggested that this might be due either to minor, non-detectable increases in GH secretion, or to direct effects of T on IGF-I concentrations. The regulatory mechanisms by which T-administration are leading to metabolic and anthropometric improvements, might be direct effects of T, with or without mediation via GH secretion.     

Individual amino acid balances in young lean and obese Zucker rats fed a cafeteria diet

The amino acid composition of the diet ingested by reference and cafeteria diet-fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet.Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids.In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age — or size — of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the blueprint for growth which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accuring protein with high rates throughout.Diet composition — and not protein availability or quality-induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity.There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both models of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization. (Mol Cell Biochem121: 45–58, 1993)     

Association between barium exposed,CYP19A1 and central obesity: A cross-sectional study in rural China

Backgroundobesity is a major risk factor for many metabolic diseases such as diabetes and cardiometabolic diseases. This study aimed to evaluate the association of plasma and urinary barium concentrations, CYP19A1 gene polymorphisms, and their interaction with central obesity in a rural Chinese population.Methodsrestricted cubic spline model was used to explore the dose-response relationship between barium and the risk of developing central obesity and waist circumference; logistic regression model was used to assess the association between barium, CYP19A1 gene polymorphisms and their interaction with central obesity.Resultsthe results of the restricted cubic spline model showed that plasma barium concentration was linearly associated with the risk of developing central obesity and non-linearly associated with waist circumference. Logistic regression analysis showed that participants with Q4 plasma barium concentration exhibited a higher risk of central obesity compared to participants with Q1 barium concentration; participants carrying the rs10046-AA gene exhibited a lower risk of central obesity than those carrying the rs10046-G(GG+GA) gene; participants carrying the rs10046-GA genotype showed 1.754 times higher risk of central obesity than those carrying rs10046-GG+AA genotype. There was a significant interaction between plasma barium and CYP19A1 gene polymorphism on central obesity.Conclusionthe development of central obesity was associated with plasma barium and CYP19A1.     

Nutrition and Physical Activity Program to Attenuate Obesity and Promote Physical and Metabolic Fitness in Elementary School Children

Obesity and low levels of physical and metabolic fitness are risk factors for cardiovascular disease and diabetes. The purpose of this investigation was to attenuate obesity and improve physical and metabolic fitness in elementary school children. Schools have the opportunity, mechanisms, and personnel in place to deliver nutrition education, fitness activities, and a school food service that is nutritious and healthy. Cohorts from grades 3 to 5 in two school districts in rural Nebraska (Intervention/Control) participated in a 2-year study of physical activity and modified school lunch program. Data collection for aerobic capacity, body composition, blood chemistry, nutrition knowledge, energy intake, and physical activity was at the beginning and end of each year. Int received enhanced physical activity, grade specific nutrition education, and a lower fat and sodium school lunch program. Con continued with a regular school lunch and team sports activity program. At year 2, Int lunches had significantly less energy (9%), fat (25%), sodium (21%), and more fiber (17%). However, measures of 24-hour energy intake for Int and Con showed significant differences for sodium only. Physical activity in the classroom was 6% greater for Int compared to Con (p < 0.05) but physical activity outside of school was ?16 % less for Int compared to Con (p < 0.05). Body weight and body fat were not different between schools for normal weight or obese children. No differences were found for cholesterol, insulin, and glucose; however, HDL cholesterol was significantly greater and cholesterol/HDL was significantly less for Int compared to Con (p < 0.05). It appears that compensation in both energy intake and physical activity outside of school may be responsible for the lack of differences between Int and Con.