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Cell Metab. 2017 Oct 3;26(4):660-671.e3. doi: 10.1016/j.cmet.2017.08.009. Epub 2017 Aug 24.

Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.

Author information

1
Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA. Electronic address: lawrence.kazak@mcgill.ca.
2
Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA.
3
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4
Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA.
5
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
6
Division of Endocrinology, Beth Israel Deaconess Medical Center and Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
7
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
8
Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA. Electronic address: bruce_spiegelman@dfci.harvard.edu.

Abstract

Diet-induced thermogenesis is an important homeostatic mechanism that limits weight gain in response to caloric excess and contributes to the relative stability of body weight in most individuals. We previously demonstrated that creatine enhances energy expenditure through stimulation of mitochondrial ATP turnover, but the physiological role and importance of creatine energetics in adipose tissue have not been explored. Here, we have inactivated the first and rate-limiting enzyme of creatine biosynthesis, glycine amidinotransferase (GATM), selectively in fat (Adipo-Gatm KO). Adipo-Gatm KO mice are prone to diet-induced obesity due to the suppression of elevated energy expenditure that occurs in response to high-calorie feeding. This is paralleled by a blunted capacity for β3-adrenergic activation of metabolic rate, which is rescued by dietary creatine supplementation. These results provide strong in vivo genetic support for a role of GATM and creatine metabolism in energy expenditure, diet-induced thermogenesis, and defense against diet-induced obesity.

KEYWORDS:

CL 316,243; brown adipose tissue; creatine; diet-induced thermogenesis; energy balance; energy expenditure; glycine amidinotransferase; obesity; thermoneutrality

PMID:
28844881
PMCID:
PMC5629120
DOI:
10.1016/j.cmet.2017.08.009
[Indexed for MEDLINE]
Free PMC Article

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