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Metformin, Aerobic Exercise, and the Combination in the Treatment of Type 2 Diabetes and NAFLD in OLETF rats
Author(s) -
Linden Melissa A,
Meers Grace M.,
Fletcher Justin A.,
Siddique Sameer,
Laughlin M. Harold,
Booth Frank W.,
Ibdah Jamal A.,
Thyfault John P.,
Rector R. Scott
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1155.2
Subject(s) - metformin , medicine , lipogenesis , steatosis , endocrinology , fatty acid synthase , nonalcoholic fatty liver disease , type 2 diabetes , fatty liver , diabetes mellitus , insulin , lipid metabolism , disease
Exercise and metformin are common therapies for type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether combining therapies offers greater benefit for T2D and NAFLD outcomes. We randomly assigned type 2 diabetic, Otsuka Long‐Evans Tokushima Fatty (OLETF) rats (age 20 wks; n=10/group) to sedentary (SED), SED + metformin (SED+MET; 300 mg/kg/day), moderate intensity exercise training (EX; 20 m/min, 60 min/d, 5 d/wk treadmill running), or EX+MET groups for 12 weeks. MET, EX and EX+MET were effective in the management of T2D and all three treatments lowered hepatic steatosis and serum markers of liver injury; however, EX lowered liver TAG content more than MET with no added benefit of combining EX + MET. Only EX animals exhibited increases in hepatic mitochondrial fatty acid oxidation, hepatic citrate synthase activity, and hepatic β‐HAD activity compared with SED (p<0.05). Furthermore, EX attenuated hepatic de novo lipogenesis markers acetyl‐CoA carboxylase, fatty acid synthase, and stearoyl‐CoA desaturase‐1 to a greater extent than MET, with no further reductions in the EX+MET group. In conclusion, EX may be a more effective treatment for NAFLD than MET and the addition of MET to EX does not appear to illicit greater improvements in the hyperphagic, obese rodent model of T2D and NAFLD. Supported by: NIH T32 AR 048523–07, DK088940 , RO1HL036088, and VHA‐CDA2 IK2BX001299–01