title: Gelatinases impart susceptibility to high-fat diet-induced obesity in mice.
abstract: Gelatinases play a role in adipose and muscle hypertrophy and could be involved in tissue remodeling in response to high-fat diet (HFD) intake. This study tested potential roles of gelatinases (matrix metalloproteinses-2 and -9 [MMP-2 and -9]) in relationship to an antigrowth factor [myostatin (MSTN)] known to be dysregulated in relation to HFD-induced obesity (HFDIO) propensity. In vitro and ex vivo analyses demonstrated that MMP-9 increased mature MSTN levels, indicating a potential role of gelatinases in MSTN activation in vivo. HFD intake resulted in increased body weight and circulating blood glucose values in C57BL/6J and MMP-9 null mice, with no changes observed in SWR/J mice. HFD intake attenuated MMP-9 and MMP-2 mRNA levels in SWR/J mice while elevating MMP-2 levels in skeletal muscle in C57BL/6J mice. In MMP-9 null mice, the effects of HFD intake were muted. Consistent with changes in mRNA levels, HFD intake increased MMP-9 activity in muscle tissue of C57BL/6J mice, demonstrating a strong relationship between HFDIO susceptibility and local MMP regulation. Overall, resistance to HFDIO appears to correspond to low MMP-9 and MSTN levels, suggesting a role of MMP-9 in MSTN activation in local tissue responses to HFD intake.
authors: Department of Biological Sciences, North Dakota State University, Fargo, ND, USA. pegbiga@uab.edu
authors: Peggy R
authors: PR
authors: Biga
authors: Jacob M
authors: JM
authors: Froehlich
authors: Kendra J
authors: KJ
authors: Greenlee
authors: Nicholas J
authors: NJ
authors: Galt
authors: Ben M
authors: BM
authors: Meyer
authors: Delci J
authors: DJ
authors: Christensen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D006984:Hypertrophy / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000473:pathology*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Gelatinase; HFDIO; High-fat diet-induced obesity; MMP-2; MMP-9; Myostatin