Omental 11beta-hydroxysteroid dehydrogenase 1 correlates with fat cell size independently of obesity.

Objectives: In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.

Lack of an effect of pioglitazone or glipizide on lipoprotein-associated phospholipase A2 in type 2 diabetes.

Objective: To study the effects of pioglitazone, a peroxisome proliferator-activated receptor-y agonist with vascular beneficial effects, and glipizide, an insulin secretagogue, on novel inflammatory vascular risk markers in subjects with and without type 2 diabetes.

Methods: We studied 11 subjects without diabetes and 19 matched subjects with diabetes. The subjects with diabetes were randomly assigned to receive either 45 mg daily of pioglitazone (N = 8) or 10 mg daily of glipizide (N = 11) (median dose) for 12 weeks.

Two years of treatment with dehydroepiandrosterone does not improve insulin secretion, insulin action, or postprandial glucose turnover in elderly men or women.

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo.

Sex differences in abdominal, gluteal, and thigh LPL activity.

Lipoprotein lipase (LPL) activity is necessary for adipocytes to take up triglycerides from the circulation, and regional differences in LPL activity could help determine regional fat storage. LPL activity has been reported to increase as a function of fat cell size, but this issue has not been extensively evaluated in different depots comparing sexes. Our objective was to determine whether sex alters the relationship between LPL activity and fat cell size.

Basal and insulin-regulated free fatty acid and glucose metabolism in humans.

These studies were done to examine the effects of body composition, resting energy expenditure (REE), sex, and fitness on basal and insulin-regulated FFA and glucose metabolism. We performed 137 experiments in 101 nondiabetic, premenopausal women and men, ranging from low normal weight to class III obese (BMI 18.0-40.

Direct free fatty acid uptake into human adipocytes in vivo: relation to body fat distribution.

We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normal-weight postabsorptive men and women.

Single-gene detection and karyotyping using small-target fluorescence in situ hybridization on maize somatic chromosomes.

Combined with a system for identifying each of the chromosomes in a genome, visualizing the location of individual genetic loci by fluorescence in situ hybridization (FISH) would aid in assembling physical and genetic maps. Previously, large genomic clones have been successfully used as FISH probes onto somatic chromosomes but this approach is complicated in species with abundant repetitive elements. In this study, repeat-free portions of sequences that were anchored to particular chromosomes including genes, gene clusters, large cDNAs, and portions of BACs obtained from public databases were used to label the corresponding physical location using FISH.

Insulin dose response analysis of free fatty acid kinetics.

Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.

Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics.

The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo+Placebo, (B) GH (2 mg daily)+Placebo, and (C) GH (2 mg daily)+Acipimox (250 mgx3 daily). In the basal state, GH (B) increased FFA levels (P<0.

Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.

Background: Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas.

Methods: 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

Background & Aims: Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers.

DHEA in elderly women and DHEA or testosterone in elderly men.

Background: Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown.

Methods: We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo.

High-precision isotopic analysis of palmitoylcarnitine by liquid chromatography/electrospray ionization ion-trap tandem mass spectrometry.

Single quadrupole gas chromatography/mass spectrometry (GC/MS) has been widely used for isotopic analysis in metabolic investigations using stable isotopes as tracers. However, its inherent shortcomings prohibit it from broader use, including low isotopic precision and the need for chemical derivatization of the analyte. In order to improve isotopic detection power, liquid chromatography/electrospray ionization ion-trap tandem mass spectrometry (LC/ESI-itMS2) has been evaluated for its isotopic precision and chemical sensitivity for the analysis of [13C]palmitoylcarnitine.

Assessment and preparation of patients for bariatric surgery.

The number of bariatric surgical procedures performed in the United States has increased steadily during the past decade. Currently accepted criteria for consideration of bariatric surgery include a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 40 kg/m2 or greater (or >35 kg/m2 with obesity-related comorbidities), documented or high probability of failure of nonsurgical weight loss treatments, and assurance that the patient is well informed, motivated, and compliant. Appropriate patient selection is important in achieving optimal outcomes after bariatric surgery.

Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease.

Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human brain. In this study, we show that sPLA2-IIA mRNA is up-regulated in Alzheimer's disease (AD) brains as compared to non-demented elderly brains (ND).

Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns.

Anatomically separate fat depots differ in size, function, and contribution to pathological states, such as the metabolic syndrome. We isolated preadipocytes from different human fat depots to determine whether the basis for this variation is partly attributable to differences in inherent properties of fat cell progenitors. We found that genome-wide expression profiles of primary preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and omental fat depots were distinct.

Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats.

Hyperinsulinemia is common in obesity, but whether it plays a role in intramyocellular triglyceride (imcTG) buildup is unknown. In this study, hyperinsulinemic-euglycemic clamp experiments were performed in overnight-fasted lean and high-fat-fed obese rats, awake, to determine the effect of insulin on imcTG synthesis (incorporation of [(14)C]glycerol, [(14)C]glucose, and [(3)H]oleate). Insulin infusion at 25 (low insulin) and 100 (high insulin) pmol/kg/min increased plasma insulin by 5- and 16-fold, respectively, whereas plasma and intramyocellular glycerol, FFAs, triglycerides, and glucose levels were maintained at their basal levels by co-infusion of exogenous glycerol, FFAs, and triglycerides at fixed rates and glucose at varying rates.

Potential role of new therapies in modifying cardiovascular risk in overweight patients with metabolic risk factors.

The serotonin, norepinephrine, dopamine, and endocannabinoid systems, as well as a host of other systems, mediate hunger and satiety signals. Weight loss agents that modulate appetite through pure central nervous system pathways (e.g.

Energy expenditure, insulin, and VLDL-triglyceride production in humans.

Hypertriglyceridemia is considered a cardiovascular risk factor in diabetic and nondiabetic subjects. In this study, we aimed to determine potential regulators of very low density lipoprotein-triglyceride (TG) production. VLDL-TG kinetics were measured in 13 men and 12 women [body mass index [mean (range)]: 24.

Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers.

Background: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone.

Methods: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone.

Sex-specific differences in leg fat uptake are revealed with a high-fat meal.

The mechanism(s) by which sex specific differences in regional body fat distribution develop are not known. We assessed the effects of a high-fat (HF) meal on fatty acid oxidation and uptake into regional fat depots using isotopic tracers and adipose biopsies. Thirty men (BMI 23.

Weekly changes in basal metabolic rate with eight weeks of overfeeding.

Objective: The contribution of basal metabolic rate (BMR) to weight gain susceptibility has long been debated. We wanted to examine whether BMR changes in a linear fashion with overfeeding. Our hypothesis was that BMR does not increase linearly with 1000-kcal/d overfeeding in lean healthy subjects over 8 weeks.

Thematic review series: patient-oriented research. Free fatty acid metabolism in human obesity.

Adipose tissue lipolysis provides circulating FFAs to meet the body's lipid fuel demands. FFA release is well regulated in normal-weight individuals; however, in upper-body obesity, excess lipolysis is commonly seen. This abnormality is considered a cause for at least some of the metabolic defects (dyslipidemia, insulin resistance) associated with upper-body obesity.

Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human model.

Objective: To review the evidence for and against the role of visceral adipose tissue as a major contributor to the metabolic complications of obesity through abnormal regulation of lipolysis.

Research Methods And Procedures: Data from investigators in the field who have studied visceral adiposity and metabolic health and/or regional and systemic free fatty acid (FFA) release were considered.

Results: Although visceral fat mass was positively correlated with adverse health consequences and excess FFA availability, visceral fat was not the source of excess systemic FFA availability.

Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes.

Objective: Pioglitazone, a peroxisome proliferator-activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups.

Research Design And Methods: We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks.