The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity.
Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high-fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high-fat diet. CD38 is a ubiquitous enzyme that catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways. We report that CD38-deficient mice are protected against high-fat diet-induced obesity owing to enhanced energy expenditure. In fact, calorimetric studies indicate that CD38-deficient animals have a higher metabolic rate compared to control mice. Analysis of the mechanism revealed that this resistance to diet-induced obesity is mediated at least in part via a NAD-dependent activation of SIRT-PGC1alpha axis, a well-established cascade, involved in the regulation of mitochondrial biogenesis and energy homeostasis. Thus, together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity.
Barbosa
Maria Thereza P
MT
Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Soares
Sandra M
SM
Novak
Colleen M
CM
Sinclair
David
D
Levine
James A
JA
Aksoy
Pinar
P
Chini
Eduardo Nunes
EN
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology / Q000209:etiology*; D015398:Signal Transduction
D004041:Dietary Fats