Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-α). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m², n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m², n = 19) compared with lean men (mean BMI: 23.4 kg/m², n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-α on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% ( P < 0.05) increase in plasma adiponectin and a 45% ( P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% ( P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-α ( P < 0.01) and IL-6 plus its soluble receptor ( P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.

Background: The consumption of sucrose-sweetened soft drinks (SSSDs) has been associated with obesity, the metabolic syndrome, and cardiovascular dis

Human adipose tissue (AT) produces several adipokines including monocyte chemoattractant protein (MCP)-1, involved in the pathogenesis of atherosclerosis. Objective: Human AT cultures, isolated adipocytes, and stromal-vascular cells were used to investigate the relationship among AT-resident macrophages, MCP-1, and adiposity and the regulation of MCP-1. Results: mRNA levels of specific macrophage markers (CD68 and CD14) are correlated with adiposity in sc AT and visceral AT (P < 0.05). MCP-1 production is higher in stromal-vascular cells vs. adipocytes (P < 0.01) and correlates with macrophage markers in both AT compartments (P < 0.05). MCP-1 release is higher in obese subjects (P < 0.05) and in VAT (P < 0.01), but after adjusting for AT-resident macrophages, the differences disappear. MCP-1 is stimulated by IL-1β, TNF-α, IL-8, IL-4, and IL-6 + IL-6-soluble receptor and is decreased by dexamethasone, IL-10, metformin, and thiazolidinediones. Discussion: MCP-1 is correlated with specific macrophage markers, adiposity, and AT localization, but the relationship seems to be related to the number of AT-resident macrophages. Despite this, MCP-1 may be involved in obesity-related health complications, and the decrease of MCP-1 by metformin and thiazolidinediones suggests that these antidiabetic compounds have antiinflammatory properties improving the low-grade inflammatory state observed in obesity.

Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.

Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation. We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in sc adipocytes. The increased number of α2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on α2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot. These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic α2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype α. These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic α2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.