Differential Responses of Visceral and Subcutaneous Fat Depots to Nutrients

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 3; pp. 672 - 678
• Main Authors: EINSTEIN, Francine H, ATZMON, Gil, YANG, Xiao-Man, MA, Xiao-Hui, RINCON, Marielisa, RUDIN, Eric, MUZUMDAR, Radhika, BARZILAI, Nir
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2005
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Coronary heart disease; Diabetes; Diabetes research; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Expression; Glucosamine - pharmacology; Glucose - metabolism; Glucose Clamp Technique; In Vitro Techniques; Insulin - pharmacology; Insulin resistance; Medical sciences; Peptides - metabolism; Rats; Risk factors; Type 2 diabetes; Endocrinopathy; Nutrient; Subcutaneous; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.3.672

Differential Responses of Visceral and Subcutaneous Fat Depots to Nutrients Francine H. Einstein 1 , Gil Atzmon 2 , Xiao-man Yang 2 , Xiao-Hui Ma 2 , Marielisa Rincon 3 , Eric Rudin 2 , Radhika Muzumdar 2 3 and Nir Barzilai 2 1 Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, New York 2 Department of Medicine, Diabetes Research and Training Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York 3 Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York Address correspondence and reprint requests to Nir Barzilai, MD, Institute for Aging Research, Belfer Bldg. #701, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. E-mail: barzilai{at}aecom.yu.edu Abstract Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats ( n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin (∼5-fold), adiponectin (∼2-fold), leptin (∼15-fold), plasminogen activating inhibitor-1 (∼10-fold), and angiotensinogen (∼4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression de-rived mainly from vascular/stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for “nutrient sensing.” Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome. FDP, fat-derived peptide GAPDH, glyceraldehyde-3-phosphate dehydrogenase HBP, hexosamine biosynthetic pathway IL, interleukin PAI-1, plasminogen activating inhibitor-1 TNF-α, tumor necrosis factor-α Footnotes F.H.E. and G.A. contributed equally to this work. Accepted November 18, 2004. Received August 5, 2004. DIABETES