Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice

• Published in: American journal of physiology: endocrinology and metabolism 2007-04, Vol.292 (4), p.E1101-E1109
• Main Authors: Turner, S. M, Roy, S, Sul, H. S, Neese, R. A, Murphy, E. J, Samandi, W, Roohk, D. J, Hellerstein, M. K
• Format: Article
• Language: English
• Subjects: Adipogenesis; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Blood Glucose - metabolism; Body Weight; Eating; Female; Food Deprivation; Gene Expression; Genes; Insulin - blood; Leptin - blood; Leptin - deficiency; Leptin - pharmacology; Lipogenesis - genetics; Lipolysis; Mice; Mice, Inbred C57BL; Mice, Obese; Mutation; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Obesity - physiopathology; Osmolar Concentration; Palmitates - metabolism; Ribonucleic acid; RNA; Rodents; Tissues; Triglycerides - biosynthesis
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00309.2005

1 Department of Nutritional Sciences and Toxicology, University of California, Berkeley; 2 Division of Endocrinology and Metabolism, Department of Medicine, San Francisco General Hospital, University of California, San Francisco; and 3 KineMed, Emeryville, California Submitted 8 July 2005 ; accepted in final form 6 November 2006 Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using 2 H 2 O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob , leptin-treated ob/ob , food-restricted ob/ob , and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 µg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux. deuterated water; lipogenesis; isotope; gene expression Address for reprint requests and other correspondence: S. M. Turner, Dept. of Nutritional Sciences & Toxicology, University of California, Berkeley, CA 94720 (e-mail: Sturner{at}KineMed.com )