Little is known about common factors (e.g., macronutrients and energy supply) regulating the protein secretory function of adipose tissue. We therefore compared the effects of randomly assigned 10-week hypoenergetic (؊600 kcal/day) diets with moderate-fat/moderate-carbohydrate or low-fat/high-carbohydrate content on circulating levels and production of proteins (using radioimmunoassays and enzyme-linked immunosorbent assays) from subcutaneous adipose tissue in 40 obese but otherwise healthy women. Similar results were obtained by the two diets. Body weight decreased by ϳ7.5%. The secretion rate of leptin decreased by ϳ40%, as did that of tumor necrosis factor-␣ (TNF-␣), and interleukin (IL)-6 and -8 decreased by 25-30%, whereas the secretion of plasminogen activator inhibitor 1 (PAI-1) and adiponectin did not show any changes. Regarding mRNA expression (by real-time PCR), only that of leptin and IL-6 decreased significantly. Circulating levels of leptin and PAI-1 decreased by 30 and 40%, respectively, but there were only minor changes in circulating TNF-␣, IL-6, or adiponectin. In conclusion, moderate caloric restriction but not macronutrient composition influences the production and secretion of adipose tissue-derived proteins during weight reduction, leptin being the most sensitive and adiponectin and PAI-1 the least sensitive. Diabetes 53: 1966 -1971, 2004 A dipose tissue secretes a number of proteins with auto-, para-, and endocrine actions, such as tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-6 and -8, plasminogen activator inhibitor 1 (PAI-1), leptin, and adiponectin (1,2). Little is known about the regulation of the protein secretory function of human adipose tissue except for leptin (3). The effect of energy restriction is of particular importance for obesity treatment (4). Dietary-induced weight loss normalizes plasma levels and adipose tissue gene expression of several adipocyte-derived proteins (5-12). Whether the same is true for protein secretion is unknown, except for TNF-␣ (5,10). Furthermore, the relative roles of loss of body fat, energy restriction per se, and changes in macronutrient supply are not known. It is also unknown which proteins are more or less sensitive to nutritional changes regarding their production by adipose tissue. These questions were investigated by studying the release of leptin, adiponectin, IL-6 and -8, TNF-␣, and PAI-1 in subcutaneous adipose tissue of 40 obese women before and after 10 weeks on moderate hypoenergetic diets with either low-fat/highcarbohydrate content or moderate-fat/moderate-carbohydrate content.
RESEARCH DESIGN AND METHODSAll subjects participated in a European multicenter study termed NutrientGene Interactions in Human Obesity: Implications for Dietary Guidelines (NUGENOB, www.nugenob.com), which examines the interaction between hypoenergetic diets and genes. Our Swedish center included 40 obese women aged 21-49 years with a BMI of 30.9 -47.7 kg/m 2 who were otherwise healthy and free of regular medication, except 1 woman who was treated wit...