Influence of Methylphenidate on Eating in Obese Men

Objective: Rapid synaptic dopamine transport or reduced brain dopamine receptor signaling may influence energy intake. Methylphenidate, a dopamine reuptake inhibitor, increases brain synaptic dopamine and produces anorexia, suggesting that it may reduce energy intake. We investigated the effects of two doses of short‐acting methylphenidate on energy intake over one meal in obese adult males. Research Methods and Procedures: Nine obese males (>85th BMI percentile) ingested a placebo or a moderate dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of methylphenidate in a within‐subject double‐blind acute laboratory study. One hour after ingestion, pizza consumption was measured in a naturalistic laboratory setting. Results: Participants reduced energy intake by 23% for the moderate dose vs. the placebo (p < 0.02), but there was no significant difference for the high dose vs. the moderate dose (p > 0.05). Participants consumed 34% fewer kilocalories after ingesting the lowest effective dose of methylphenidate compared with placebo (725.7 ± 404.5 vs.1095 ± 271.1 kcal, p < 0.01). Seven of nine subjects responded to the moderate dose. The increase in perceived drug effect above placebo was correlated with the reduction in energy intake for both the moderate (r = ?0.85, p = 0.004) and the high (r = ?0.75 p = 0.021) doses. Hunger scores were not different across drug doses or placebo before drug administration. Discussion: Methylphenidate reduced energy intake of a highly palatable food over one meal by one‐third in obese adult males. Dopamine transport inhibition may be an effective component of a comprehensive treatment for obesity.     

Lipolysis in Intraabdorninal Adipose Tissues of Obese Women and Men

Intraabdominal fat in humans is located in two major depots, the omental and mesenteric. We compared basal and stimulated lipolysis in adipose tissue from these two depots and the subcutaneous abdominal depot of obese women and men. Omental fat cells of women are smaller and have lower rates of basal lipolysis than in men. Basal Iipolysis rates are significantly higher in subcutaneous than intraabdominal adipose tissues of both genders. In men, the incremental lipolytic response to norepinephrine is significantly greater in both intraabdominal fat depots than in the subcutaneous fat, while in women tlie response of tlie mesenteric is lower than tlie omental. In women, but not men, responsiveness to tlie beta agonist isoproterenol is also increased in omental tissue. Thus, in women, omental and mesenteric adipose tissues show distinctly different metabolic properties which may moderate the impact of intraabdominal obesity.     

Sex Hormones and Sexual Function in Obese Men Losing Weight

Objective: To study the impact of a weight‐loss program on sex hormones and sexual function among 38 middle‐aged obese men (BMI ≥35 kg/m²). Research Methods and Procedures: A randomized controlled clinical trial was conducted. The treatment group (n = 19) participated in a 4‐month weight‐loss program including 10 weeks on a very‐low‐energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n = 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time‐points during follow‐up. Results: The mean weight loss in the treatment group was 21 kg at the end of the 10‐week VLED. At the end of follow‐up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormone‐binding globulin, testosterone, and high‐density lipoprotein‐cholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow‐up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group. Discussion: We conclude that obese men lose weight and increase their serum testosterone level on a weight‐loss program with VLED and behavior modification. However, they do not change their sexual function scores.     

Validation of DXA Body Composition Estimates in Obese Men and Women

The aim of this study was to determine the accuracy of dual‐energy X‐ray absorptiometry (DXA)‐derived percentage fat estimates in obese adults by using four‐compartment (4C) values as criterion measures. Differences between methods were also investigated in relation to the influence of fat‐free mass (FFM) hydration and various anthropometric measurements. Six women and eight men (age 22–54 years, BMI 28.7–39.9 kg/m², 4C percent body fat (%BF) 31.3–52.6%) had relative body fat (%BF) determined via DXA and a 4C method that incorporated measures of body density (BD), total body water (TBW), and bone mineral mass (BMM) via underwater weighing, deuterium dilution, and DXA, respectively. Anthropometric measurements were also undertaken: height, waist and gluteal girth, and anterior‐posterior (A‐P) chest depth. Values for both methods were significantly correlated (r² = 0.894) and no significant difference (P = 0.57) was detected between the means (DXA = 41.1%BF, 4C = 41.5%BF). The slope and intercept for the regression line were not significantly different (P > 0.05) from 1 and 0, respectively. Although both methods were significantly correlated, intraindividual differences between the methods were sizable (4C‐DXA, range = ?3.04 to 4.01%BF) and significantly correlated with tissue thickness (chest depth) or most surrogates of tissue thickness (body mass, BMI, waist girth) but not FFM hydration and gluteal girth. DXA provided cross‐sectional %BF data for obese adults without bias. However, individual data are associated with large prediction errors (±4.2%BF). This error appears to be associated with tissue thickness indicating that the DXA device used may not be able to accurately account for beam hardening in obese cohorts.     

Physical Frailty and Body Composition in Obese Elderly Men and Women

Objective: To evaluate the prevalence of frailty and interrelationships among body composition, physical function, and quality of life in community‐dwelling obese elderly (OE) persons. Research Methods and Procedures: Fifty‐two OE, 52 nonobese frail, and 52 nonobese nonfrail subjects, matched for age and sex, were studied. Subjective and objective measures of functional status were evaluated by using the physical performance test, exercise stress test, lower extremity (LE) strength, gait speed, static and dynamic balance, functional status questionnaires, and health‐related quality‐of‐life questionnaire (Medical Outcomes Short Form). Body composition was evaluated by using DXA, and muscle quality was evaluated by determining the ratio of LE strength to LE lean mass. Results: Among OE subjects, 96% met our standard criteria for mild to moderate frailty. Compared with the nonobese nonfrail group, the OE and nonobese frail groups had lower and similar scores in physical performance test, peak aerobic power, and functional status questionnaire, and exhibited similar impairments in strength, walking speed, balance, and health‐related quality of life. Although absolute fat‐free mass (FFM) was greater, the percentage body weight as FFM and muscle quality was lower in the OE group than in the other two groups. Discussion: Physical frailty, which predisposes to loss of independence, is common in community‐living OE men and women. Physical frailty in OE subjects was associated with low percentage FFM, poor muscle quality, and decreased quality of life. These findings suggest that weight loss therapy may be particularly important in OE persons to improve physical function, in addition to improving the medical complications associated with obesity.     

Cardiac Autonomic Nervous System Activity in Obese and Never-Obese Young Men

ARONNE, LOUIS J, RONALD MACKINTOSH, MICHAEL ROSENBAUM, RUDOLPH L LEIBEL, JULES HIRSCH. Cardiac autonomic nervous system activity in obese and never-obese young men. Autonomic nervous system (ANS) activity in age-matched, weight-stable, free-living, ad libitumfed, obese (OB) and never-obese (NO) young men (body mass index means [SD], 38.5 [3.9] and 22.0 [1.7], respectively) was evaluated by sequential blockade of cardiac autonomic innervation with weight-adjusted doses of parasympathetic (atropine) and sympathetic (esmolol) blockers so as to produce maximal effects on heart rate. Change in heart period (interbeat interval) from baseline, induced by atropine, defined parasympathetic control (PC), and the subsequent change, after esmolol administration, defined sympathetic control (SC). The heart period, after PC and SC blockade, defined intrinsic heart period (I). In the OB group, baseline heart period and PC were lower, and SC and I were higher, than in the NO group. The results in the OB, relative to the NO subjects, are similar to those reported in a previous study of NO subjects who had undergone a 10% weight gain by overfeeding. These findings suggest that the ANS of individuals with obesity is chronically altered in a way that would tend to oppose their excessive adiposity, and that these autonomic changes are more likely to be responses to other forces that induce obesity, rather than being primary agents in the production of the disease.     

High Expression of Complement Components in Omental Adipose Tissue in Obese Men

Objective: Accumulation of visceral fat is recognized as a predictor of obesity‐related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. Research Methods and Procedures: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real‐time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. Results: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue (～2‐, 4‐, 17‐, 10‐, and 7‐fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). Discussion: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra‐abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.     

Effects of Insulin on Ketogenesis Following Fasting in Lean and Obese Men

The ketone bodies (KBs) D‐3‐hydroxybutyrate (D‐3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance. The dose–response relationship between insulin and KBs was demonstrated to be shifted to the right in type 2 diabetes patients. However, KB levels have also been reported to be decreased in obesity. We investigated the metabolic adaptation to fasting with respect to glucose and KB metabolism in lean and obese men without type 2 diabetes using stable glucose and D‐3HB isotopes in a two‐step pancreatic clamp after 38 h of fasting. We found that D‐3HB fluxes in the basal state were higher in lean compared to obese men: 15.2 (10.7–27.1) vs. 7.0 (3.5–15.1) µmol/kg lean body mass (LBM)·min, respectively, P < 0.01. No differences were found in KB fluxes between lean and obese volunteers during the pancreatic clamp (step 1: 6.9 (1.8–12.0) vs. 7.4 (4.2–17.8) µmol/kg LBM·min, respectively; and step 2: 2.9 (0–7.2) vs. 3.4 (0.85–18.7) µmol/kg LBM·min, respectively), despite similar plasma insulin levels. Meanwhile, peripheral glucose uptake was higher in lean compared to obese men (step 1: 15.2 (12.3–25.6) vs. 14.7 (11.9–22.7) µmol/kg LBM·min, respectively, P ≤ 0.05; and step 2: 12.5 (7.0–17.3) vs. 10.8 (5.2–15.0) µmol/kg LBM·min, respectively, P ≤ 0.01). These data show that obese subjects who display insulin resistance on insulin‐mediated peripheral glucose uptake have the same sensitivity for the insulin‐mediated suppression of ketogenesis. This implies differential insulin sensitivity of intermediary metabolism in obesity.     

Moderate Exercise and Fibrinolytic Potential in Obese Sedentary Men with Metabolic Syndrome

Objective: To investigate the impact of 30‐minute walking exercise at 70% Vo _2max on tissue plasminogen activator (t‐PA) Ag and plasminogen activator inhibitor type 1 (PAI‐1) Ag in obese sedentary males. Research Methods and Procedures: A controlled observational study of the effect of a 30‐minute acute exercise bout at 70% Vo _2max on plasma t‐PA antigen and PAI‐1 antigen in 10 obese sedentary males matched for age, ethnic origin, and smoking status with 10 nonobese sedentary male controls. Results: The obese group remained hypofibrinolytic compared with the nonobese group at all time‐points before, during, and after exercise. t‐PA increased in both groups with exercise before returning to baseline values 30 minutes after exercise. PAI‐1 did not significantly change in either group with exercise but rose significantly 30 minutes after exercise in the obese group. Discussion: The reduction in fibrinolytic potential in the obese group represents an increase in acute thrombotic risk and could account for the increased incidence of exercise‐associated myocardial infarction observed in sedentary obese groups.     

Relationships of Plasma Leptin Levels to Changes in Plasma Free Fatty Acids in Women Who Are Lean and Women Who Are Abdominally Obese

HENNES, MAGDA MI, ARNAVAZ DUA, DIANA L MAAS, GABRIELE E SONNENBERG, GLENN R KRAKOWER, AHMED H KISSEBAH. Relationships of plasma leptin levels to changes in plasma free fatty acids in women who are lean and women who are abdominally obese. Regulation of leptin production by the hormonal and metabolic milieu is poorly understood. Because abdominal obesity is commonly associated with elevated plasma free fatty acid (FFA) flux, we examined the effects of augmenting FFA on plasma leptin levels in women who were lean and of suppressing FFA in women with abdominal obesity. In study 1, nine subjects who were lean, after a 12-hour overnight fast, received either intravenous saline or Intralipid plus heparin to increase the plasma FFA concentration to approximately 1000 μmol/ L. After 3 hours of additional fasting, subjects underwent 3-hour hyperglycemic clamps. In study 2, seven subjects with abdominal obesity were evaluated by a similar protocol, but lipolysis and plasma FFA flux were instead maximally suppressed by acipimox. In the individuals who were lean, leptin levels were unchanged during clamping. Increasing plasma FFA reduced plasma leptin from 7.66 ± 0.66 to 7.05 ±0 0.66 (p=0.03), but 3 hours of hyperglycemia plus hyperinsulinemia had no additional effect on leptin levels (7.15 ± 0.71). Basal leptin levels, 4-fold higher in the subjects with obesity, were reduced from 34.6 ± 2.4 μg/L to 32.3 ± 1.1 μg/L (p=0.004) during the clamp period. When plasma FFA flux was suppressed, however, plasma leptin levels after clamped hyperglycemia/hyperinsulinemia were increased to 38.9 ± 1.2 μg/L (p=0.014 vs. time 0 and 0.001 vs. saline protocol). Changes in leptin concentrations are not correlated with changes in FFA. These results suggest that plasma FFA concentration does not regulate plasma leptin levels in basal, extended fasting, or hyperglycemic/hyperinsulinemic states.     

Bone Mass and the CAG and GGN Androgen Receptor Polymorphisms in Young Men

Background

To determine whether androgen receptor (AR) CAG (polyglutamine) and GGN (polyglycine) polymorphisms influence bone mineral density (BMD), osteocalcin and free serum testosterone concentration in young men.

Methodology/Principal Findings

Whole body, lumbar spine and femoral bone mineral content (BMC) and BMD, Dual X-ray Absorptiometry (DXA), AR repeat polymorphisms (PCR), osteocalcin and free testosterone (ELISA) were determined in 282 healthy men (28.6±7.6 years). Individuals were grouped as CAG short (CAG_S) if harboring repeat lengths of ≤21 or CAG long (CAG_L) if CAG >21, and GGN was considered short (GGN_S) or long (GGN_L) if GGN ≤23 or >23. There was an inverse association between logarithm of CAG and GGN length and Ward''s Triangle BMC (r = −0.15 and −0.15, P<0.05, age and height adjusted). No associations between CAG or GGN repeat length and regional BMC or BMD were observed after adjusting for age. Whole body and regional BMC and BMD values were similar in men harboring CAG_S, CAG_L, GGN_S or GGN_L AR repeat polymorphisms. Men harboring the combination CAG_L+GGN_L had 6.3 and 4.4% higher lumbar spine BMC and BMD than men with the haplotype CAG_S+GGN_S (both P<0.05). Femoral neck BMD was 4.8% higher in the CAG_S+GGN_S compared with the CAG_L+GGN_S men (P<0.05). CAG_S, CAG_L, GGN_S, GGN_L men had similar osteocalcin concentration as well as the four CAG-GGN haplotypes studied.

Conclusion

AR polymorphisms have an influence on BMC and BMD in healthy adult humans, which cannot be explained through effects in osteoblastic activity.     

Testosterone Levels and Androgen Receptor Gene Polymorphism Predict Specific Symptoms of Depression in Young Men

BackgroundTestosterone (T) has been hypothesized to modulate the expression of depressive symptoms in men; however, support for this proposition is mixed.ObjectiveTo investigate bioavailable T, measured from saliva, and androgen receptor gene (AR) polymorphism (the number of glutamine [CAG] repeats in exon 1 of AR) and their relation to discrete symptoms of depression in 150 men aged 17 to 27 years who varied in mood status from depressed to nondepressed.MethodsParticipants completed the Center for Epidemiologic Studies Depression Scale and the Patient Health Questionnaire-9. Principal components analysis of the scales identified 5 factors: Negative Affect, Social/Evaluative, Cognitive, Sleep, and Appetite.ResultsAcross the sample as a whole, higher ratings on sleep symptoms of depression were predicted by lower T concentrations and shorter CAG lengths. The association between T, CAG length, and sleep symptoms was confirmed among the subgroup of men who reported moderate to severe depression. In this subgroup, CAG repeats and T concentrations also emerged as significant predictors of negative affect scores, with the number of CAG repeats making the primary contribution.ConclusionsThese findings suggest that androgens may influence specific symptoms of depression in men.     

Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men

Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI ≥ 26 kg/m²) men. Research Methods and Procedure: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double‐blind, placebo‐controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12‐week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 ± 33.77% in the forskolin group compared with a decrease of 1.08 ± 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12‐week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.     

Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men

Context

Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified.

Objective

To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal.

Design

Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5–40.2 kg/m²) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL₁ and VLDL₂) were measured after the fat-rich meal.

Main Outcome Measures

Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.

Results

The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest.

Conclusions

In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.     

Withdrawal Depression in Obese Patients after Fenfluramine Treatment

Measurements of subjective feeling in 20 patients receiving fenfluramine alternating with placebo and in 19 patients receiving phentermine alternating with placebo indicated that depression of mood occurred four days after fenfluramine withdrawal but no such depression was seen with phentermine.     

Effects of Bisphosphonates on Bone of Osteoporotic Men With Different Androgen Levels: A Case-Control Study

ObjectiveOsteoporosis in men has been neglected despite its association with disability and mortality. We evaluated the effect of bisphosphonates (BPs) on bone mineral density (BMD) and bone turnover biomarkers of osteoporotic men with different androgen levels.MethodsThis case-control study included 136 osteoporotic men who were divided into normal group (n = 75) and hypogonadism group (n = 61) (patients treated with testosterone were excluded) according to their serum testosterone levels (cutoff value, 350 ng/dL). BMD, serum testosterone, total alkaline phosphatase, and cross-linked C-telopeptide of type I collagen were detected. The relationship between testosterone levels and BMD at baseline was evaluated. All patients were treated with BPs for 2 years. We compared the effects of BPs on BMD and bone turnover biomarkers between the 2 groups.ResultsAt baseline, there were no significant differences in BMD and bone turnover biomarkers between the 2 groups. Testosterone levels were positively correlated with BMD in the hypogonadism group. After treatment, the lumbar BMD increased by 7.65% ± 1.54% and 7.47% ± 1.88% in normal and hypogonadism groups, respectively (both P < .01 vs baseline) and hip BMD increased without significant differences between the 2 groups. Serum cross-linked C-telopeptide of type I collagen and alkaline phosphatase levels decreased without significant differences between the 2 groups (all P < .01 vs baseline).ConclusionTestosterone level is positively correlated with BMD in men with hypogonadism. In osteoporotic men, BPs significantly increase spine and hip BMD and decrease bone resorption. The efficacy of BPs is similar in men with or without hypogonadism.     

The Effects of Metformin and Diet on Plasma Testosterone and Leptin Levels in Obese Men

Objective: The aim of this study was to investigate the effects of combined hypocaloric diet and metformin on circulating testosterone and leptin levels in obese men with or without type 2 diabetes. Research Methods and Procedures: Twenty obese men with type 2 diabetes (mean body mass index [BMI]: 35.5 ± 1.1 kg/m²) and 20 nondiabetic obese men were enrolled in the study. We measured serum follicle‐stimulating hormone, luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), sex‐hormone‐binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and plasma leptin levels before and 3 months after metformin treatment. Both groups were placed on a hypocaloric diet and 850 mg of metformin taken orally twice daily for 3 months. Results: Metformin and hypocaloric diets led to decreases in BMI and waist and hip circumferences in both groups. A significant decrease in TT levels in the diabetic group and FT levels in the control group was found, whereas follicle‐stimulating hormone, LH, and DHEAS levels were not changed significantly. A significant increase in SHBG levels was observed in the control group but not in the patient group. Leptin levels also decreased after treatment in both groups. Decreased testosterone levels were not correlated to changes in waist and hip circumference, waist‐to‐hip ratio, BMI, and levels of fasting blood glucose, leptin, SHBG, or DHEAS in the diabetic group. However, a decrease in FT was correlated to changes in the levels of SHBG (r = ?0.71, p = 0.001) and LH (r = 0.80, p = 0.001) but not to other parameters. Discussion: We conclude that metformin treatment combined with a hypocaloric diet leads to reduced FT levels in obese nondiabetic men and to reduced TT levels in obese men with type 2 diabetes. Increased SHBG levels may account for the decrease in FT levels in the former group.     

Effects of the FABP2 A54T Mutation on Triglyceride Metabolism of Viscerally Obese Men

Objective: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition. Research Methods and Procedures: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism. Results: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High‐density lipoprotein (HDL)‐TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL‐TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG‐rich lipoproteins (large‐TRL; S_f > 400) were correlated with HDL‐TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only. Discussion: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.     

Fat Compartments and Apolipoprotein B‐100 Kinetics in Overweight‐Obese Men

Objective: To examine the association between the kinetics of very‐low‐density‐lipoprotein (VLDL)‐apolipoprotein B‐100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men. Research Methods and Procedures: Hepatic secretion of VLDL was measured using an intravenous infusion of 1‐[¹³C]‐leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m²). Isotopic enrichment of VLDL‐apoB was measured using gas chromatography‐mass spectrometry and a multicompartmental model used to estimate VLDL‐apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. Results: In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL‐apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL‐apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL‐apoB secretion after adjusting for TATM or HOMA score (r = 0.360, p < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL‐apoB after adjusting for HOMA score. Discussion: In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL‐apoB. The effect of IPATM on VLDL‐apoB secretion is independent of both total fat mass and the degree of insulin resistance.