Expression of Lipolytic Genes in Adipose Tissue Is Differentially Regulated During Multiple Phases of Dietary Intervention in Obese Women

The aim of this study was to investigate the time-course of the expression of key lipolysis-regulating genes in the subcutaneous adipose tissue (SCAT) during different phases of a 6-month dietary intervention. Fifteen obese women (BMI 34.7+/-1.0 kg.m(-2)) underwent a 6-month dietary intervention consisting of 1 month very low calorie diet (VLCD), followed by 2 months low calorie diet (LCD) and 3 months weight maintenance diet (WM). At each phase of the dietary intervention, a needle microbiopsy of the abdominal SCAT was obtained to evaluate mRNA expression of key lipolysis-regulating genes and a hyperinsulinemic euglycemic clamp (HEC) was performed. Dietary intervention induced a body weight reduction of 9.8 % and an improvement of insulin sensitivity as assessed by a HEC. Compared to pre-diet levels, mRNA levels of the adrenergic beta(2)-receptor in SCAT were higher at the end of VLCD and not different at the end of LCD and WM. In contrast, the expression of the adrenergic alpha(2)-receptor was lower at the end of VLCD and LCD compared to the pre-diet levels and did not differ at WM. Adipose triglyceride lipase and hormone-sensitive lipase levels were lower than the pre-diet levels at the end of LCD only, while phosphodiesterase-3B and the insulin receptor levels did not change throughout the dietary intervention. The results suggest that the regulation pattern of the genes that are involved in the control of lipolysis is different at the respective phases of the dietary intervention and depends on the duration of the diet and the status of energy balance.status: publishe

Apolipoprotein M:a novel adipokine decreasing with obesity and upregulated by calorie restriction

Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases