CYR61 polymorphisms are associated with plasma HDL-cholesterol levels in obese individuals.

We have recently characterized the transcriptome of the omental adipose tissue of non-diabetic, obese men with and without the metabolic syndrome (MS). The cysteine-rich protein 61 (CYR61) is one of the most differentially expressed genes between the groups and has been selected for a detailed molecular investigation. Direct sequencing of complete CYR61 gene revealed five polymorphisms with minor allele frequency >5% in the promoter region (rs 3753794, rs 3753793 and rs 2297140), intron 1 (rs 2297141) and intron 2 (IVS 2+50).

Visceral adipocytes and the metabolic syndrome.

Recently, the high responsiveness of omental adipocytes to positive lipolytic stimuli has been clearly demonstrated in women. We conclude that adipose tissue fatty acid release, storage capacity, and secreted cytokines may all be involved in the etiology of the metabolic syndrome. The anatomical location of visceral adipocytes close to the liver, combined with possible depot-specific alterations in various adipocyte or adipose tissue features likely play critical roles in this process.

Metabolic action of peroxisome proliferator-activated receptor gamma agonism in rats with exogenous hypercorticosteronemia.

Objective: The beneficial metabolic actions of peroxisome proliferator-activated receptor gamma (PPARgamma) agonism are associated with modifications in adipose tissue metabolism that include a reduction in local glucocorticoid (GC) production by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). This study aimed to assess the contribution of GC attenuation to PPARgamma agonism action on gene expression in visceral adipose tissue and global metabolic profile.

Design: Rats were treated (2 weeks) with the PPARgamma agonist rosiglitazone (RSG, 10 mg/kg/day) with concomitant infusion of vehicle (cholesterol implant) or corticosterone (HiCORT, 75 mg/implant/week) to defeat PPARgamma-mediated GC attenuation.

ZFP36: a promising candidate gene for obesity-related metabolic complications identified by converging genomics.

Background: Few genes have been associated with the metabolic syndrome (MS), although its genetic component is well accepted. The aim of this study was to compare the adipose tissue gene expression profiles of obese men with and without the MS and to apply an integrative genomic approach to propose new candidate genes.

Methods: Affymetrix HG-U133 plus 2 arrays have been used for expression profiling of omental adipose tissue of non-diabetic obese men with (n=7) and without (n=7) the MS, as defined by the NCEP-ATPIII, that undergo a bariatric operation.

Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis.

The rates of coronary disease have accelerated dramatically amongst South Asians, driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes that have become so common amongst them. These precursors of vascular disease appear at lower absolute amounts of adipose tissue in South Asians than in whites. In this paper, we set out a new hypothesis--the adipose tissue overflow hypothesis--to account for these findings.

Regional differences in adipose tissue metabolism in obese men.

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.

Androgen inactivation and steroid-converting enzyme expression in abdominal adipose tissue in men.

We examined 5alpha-dihydrotestosterone (5alpha-DHT) inactivation and the expression of several steroid-converting enzymes with a focus on aldoketoreductases 1C (AKR1C), especially AKR1C2, in abdominal adipose tissue in men. AKR1C2 is mainly involved in the conversion of the potent androgen 5alpha-DHT to its inactive forms 5alpha-androstane-3alpha/beta,17beta-diol (3alpha/beta-diol). Subcutaneous (s.

Effect of age on skeletal muscle myofibrillar mRNA abundance: relationship to myosin heavy chain protein synthesis rate.

Age-related changes in myosin heavy chain (MHC) phenotype impact both the quantity and functional character of skeletal muscle. The present study was undertaken to examine the hypothesis that age-related changes in MHC mRNA abundance underlie alterations in protein synthesis rates and content. We measured the abundance of mRNA for MHC isoforms (MHC I, MHC IIa, IIx) and actin by RT-PCR in 6 young (mean +/- SE; 29 +/- 3) and 12 elderly (73 +/- 1 yr; P<0.

Visceral adiposity and endothelial lipase.

Context: Overexpression of endothelial lipase (EL) has been shown to reduce plasma high-density lipoprotein cholesterol levels in animal models. However, the extent to which EL contributes to modulate the deteriorated high-density lipoprotein profile observed in obesity in humans is less clear.

Objectives: The objectives of this study were to investigate the association between levels of obesity and visceral adiposity in particular and plasma EL concentrations.

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.

Circulating progesterone and obesity in men.

Progesterone can be detected in male plasma and has been considered to originate mainly from the adrenals. We have examined the association between circulating progesterone and obesity in a sample of thirty-eight lean to morbidly obese men aged 44.5 +/- 9.

Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution.

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP-stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery.

Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones.

Chronic heart failure is characterized by changes in skeletal muscle that contribute to exercise intolerance and muscle weakness. To determine whether changes in the quantity and isoform distribution of key myofibrillar proteins are related to altered gene expression, we measured skeletal muscle myofibrillar mRNA abundance in nine heart failure patients (mean +/- SE; 63 +/- 3 yr) and nine controls (70 +/- 3 yr). In addition, we assessed the relationship of circulating levels of anabolic and catabolic hormones, as well as local expression of insulin-like growth factor (IGF)-I, to myofibrillar mRNA abundance.

Contribution of age and declining androgen levels to features of the metabolic syndrome in men.

Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both decline with age in healthy men. Features of the metabolic syndrome also show age-related deteriorations. We examined the relative contribution of age and declining androgen levels to features of the metabolic syndrome in men.

Effect of an oat bran-rich supplement on the metabolic profile of overweight premenopausal women.

Background/aims: A healthy diet is a key factor in the prevention of cardiovascular disease, the leading cause of death for women in industrialized countries. In this regard, soluble fibers may have beneficial effects on the plasma lipoprotein/lipid profile. The objective of the present study was to investigate the plasma lipoprotein/lipid response to dietary fibers in overweight premenopausal women within a randomized controlled trial.

The peroxisome proliferator-activated receptor alpha Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men.

Background: Serum lipid responses to dietary modification are partly determined by genetic factors.

Objective: We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men.

Design: Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI).

Molecular screening of the 11beta-HSD1 gene in men characterized by the metabolic syndrome.

Adipose tissue type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), which generates hormonally active cortisol from inactive cortisone, has been shown to play a central role in adipocyte differentiation and abdominal obesity-related metabolic complications. The objective was to investigate whether genetic variations in the human 11beta-HSD1 gene are associated with the metabolic syndrome among French-Canadian men. We sequenced all exons, the exon-intron splicing boundaries, and 5' and 3' regions of the human 11beta-HSD1 gene in 36 men with the metabolic syndrome, as defined by the National Cholesterol Education Program-Adult Treatment Panel III, and two controls.

Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women.

We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha-HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal subcutaneous and omental adipose tissue biopsies were obtained during abdominal hysterectomies in seven women with low visceral adipose tissue (VAT) area and seven age- and total body fat mass-matched women with visceral obesity.

Expression and activity of 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in abdominal subcutaneous and omental adipose tissue in women.

We examined the expression and activity of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in abdominal adipose tissue in women. This recently characterized enzyme from the aldoketoreductase 1C family is responsible for the conversion of progesterone into 20alpha-hydroxyprogesterone. Abdominal sc (SC) and omental (OM) adipose tissue biopsies were obtained from a sample of 32 women aged 47.

A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men.

Adipose tissue located within the abdominal cavity has been suggested to be functionally and metabolically distinct from that of the subcutaneous compartment. These differences could play a role in obesity-related complications. The aim of this study was to compare gene expression profiles of subcutaneous and visceral adipose tissues of 10 nondiabetic, normolipidemic obese men.

Association between the PPARalpha-L162V polymorphism and components of the metabolic syndrome.

Genetic factors, alone or in interaction with components of the diet, are thought to be involved in the development of the metabolic syndrome. The objective of our study was first to compare the frequency of the peroxisome proliferator-activated receptor (PPAR)alpha-L162V polymorphism in a sample of men with and without the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and secondly, to evaluate gene-diet interaction effects on features of the metabolic syndrome. The PPARalpha-L162V genotype was determined in a sample of 632 men by a polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based method; fat as well as saturated fat intakes were evaluated by a dietitian-administered food frequency questionnaire.

Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids.

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists improve insulin sensitivity and lipemia partly through enhancing adipose tissue proliferation and capacity for lipid retention. The agonists also reduce local adipose glucocorticoid production, which may in turn contribute to their metabolic actions. This study assessed the effects of a PPARgamma agonist in the absence of glucocorticoids (adrenalectomy, ADX).

Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies.

The age-related decline in serum dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) has suggested that a relative deficiency of these steroids may be causally related to the development of chronic diseases generally associated with aging, including insulin resistance, obesity, cardiovascular disease, cancer, reductions of the immune defense, depression and a general deterioration in the sensation of well-being. The numerous studies which have focused on the link between DHEA and cardiovascular disease have generally been inconsistent, generating much debate and controversy on this issue. The present article is an analysis of studies on the relationship between endogenous DHEA or DHEA-S, obesity and cardiovascular disease risk, as well as DHEA treatment studies.

Ovarian hormone status and abdominal visceral adipose tissue metabolism.

We examined abdominal sc and visceral adipose tissue metabolism in a sample of 19 regularly cycling premenopausal women (age 46.3 +/- 3.7 yr) and 10 women with natural menopause or pharmacological ovarian suppression (age 51.

Plasma lipoprotein profile in the male cynomolgus monkey under normal, hypogonadal, and combined androgen blockade conditions.

In men, orchiectomy (GDX) produces an atherogenic lipid profile, whereas combined androgen blockade (CAB) induces a favorable lipid pattern. To better understand the opposite effects of GDX and CAB on lipid metabolism, we have compared the changes in plasma lipoproteins, mesenteric fat metabolism, as well as serum and intratissular sex steroid concentrations in intact, GDX, and GDX+FLU [GDX male cynomolgus monkeys treated for 3 months with flutamide (FLU)]. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenediol remained stable after GDX.