Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates

• Published in: American journal of physiology: endocrinology and metabolism Vol. 298; no. 1; pp. E108 - E116
• Main Authors: Bruss, Matthew D, Khambatta, Cyrus F, Ruby, Maxwell A, Aggarwal, Ishita, Hellerstein, Marc K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2010
• Subjects: Adipose Tissue - metabolism; Animals; Body fat; Caloric Restriction; Deuterium; Diet; Eating - physiology; Energy Metabolism - physiology; Fatty acids; Fatty Acids - biosynthesis; Fatty Acids - metabolism; Fatty Acids, Monounsaturated - metabolism; Fatty Acids, Nonesterified - blood; Gene Expression - physiology; Lipogenesis - physiology; Male; Mice; Mice, Inbred C57BL; Models, Biological; Oxidation; Oxidation-Reduction; Oxidative Stress - physiology; Protein synthesis; Rodents; Signal Transduction - physiology; Tissues; Triglycerides - blood
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00524.2009

1 Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley; and 2 Children's Hospital Oakland Research Institute, Oakland, California Submitted 25 August 2009 ; accepted in final form 2 November 2009 Calorie restriction (CR) increases longevity and retards the development of many chronic diseases, but the underlying metabolic signals are poorly understood. Increased fatty acid (FA) oxidation and reduced FA synthesis have been hypothesized to be important metabolic adaptations to CR. However, at metabolic steady state, FA oxidation must match FA intake plus synthesis; moreover, FA intake is low, not high, during CR. Therefore, it is not clear how FA dynamics are altered during CR. Accordingly, we measured food intake patterns, whole body fuel selection, endogenous FA synthesis, and gene expression in mice on CR. Within 2 days of CR being started, a shift to a cyclic, diurnal pattern of whole body FA metabolism occurred, with an initial phase of elevated endogenous FA synthesis [respiratory exchange ratio (RER) >1.10, lasting 4–6 h after food provision], followed by a prolonged phase of FA oxidation (RER = 0.70, lasting 18–20 h). CR mice oxidized four times as much fat per day as ad libitum (AL)-fed controls (367 ± 19 vs. 97 ± 14 mg/day, P < O.001) despite reduced energy intake from fat. This increase in FA oxidation was balanced by a threefold increase in adipose tissue FA synthesis compared with AL. Expression of FA synthase and acetyl-CoA carboxylase mRNA were increased in adipose and liver in a time-dependent manner. We conclude that CR induces a surprising metabolic pattern characterized by periods of elevated FA synthesis alternating with periods of FA oxidation disproportionate to dietary FA intake. This pattern may have implications for oxidative damage and disease risk. fat synthesis; lipogenesis; palmitoleate; heavy water Address for reprint requests and other correspondence: M. D. Bruss, Dept. of Nutritional Sciences and Toxicology, Univ. of California at Berkeley, Morgan Hall, Rm. 309, Berkeley, CA 94720-3104 (e-mail: mattbruss{at}berkeley.edu ).