title: Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats.
abstract: Here, we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (age: 20 wk, hyperglycemic and hyperinsulinemic; n = 10/group) were randomly assigned to sedentary (O-SED), SED plus metformin (O-SED + M; 300 mg·kg(-1)·day(-1)), moderate-intensity exercise training (O-EndEx; 20 m/min, 60 min/day, 5 days/wk treadmill running), or O-EndEx + M groups for 12 wk. Long-Evans Tokushima Otsuka (L-SED) rats served as nonhyperphagic controls. O-SED + M, O-EndEx, and O-EndEx + M were effective in the management of type 2 diabetes, and all three treatments lowered hepatic steatosis and serum markers of liver injury; however, O-EndEx lowered liver triglyceride content and fasting hyperglycemia more than O-SED + M. In addition, exercise elicited greater improvements compared with metformin alone on postchallenge glycemic control, liver diacylglycerol content, hepatic mitochondrial palmitate oxidation, citrate synthase, and β-HAD activities and in the attenuation of markers of hepatic fatty acid uptake and de novo fatty acid synthesis. Surprisingly, combining metformin and aerobic exercise training offered little added benefit to these outcomes, and in fact, metformin actually blunted exercise-induced increases in complete mitochondrial palmitate oxidation and β-HAD activity. In conclusion, aerobic exercise training was more effective than metformin administration in the management of type 2 diabetes and NAFLD outcomes in obese hyperphagic OLETF rats. Combining therapies offered little additional benefit beyond exercise alone, and findings suggest that metformin potentially impairs exercise-induced hepatic mitochondrial adaptations.
authors: Research Service, Harry S. Truman Memorial Veterans Affairs Hospital;
authors: Melissa A
authors: MA
authors: Linden
authors: Justin A
authors: JA
authors: Fletcher
authors: E Matthew
authors: EM
authors: Morris
authors: Grace M
authors: GM
authors: Meers
authors: Monica L
authors: ML
authors: Kearney
authors: Jacqueline M
authors: JM
authors: Crissey
authors: M Harold
authors: MH
authors: Laughlin
authors: Frank W
authors: FW
authors: Booth
authors: James R
authors: JR
authors: Sowers
authors: Jamal A
authors: JA
authors: Ibdah
authors: John P
authors: JP
authors: Thyfault
authors: R Scott
authors: RS
authors: Rector
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000628:therapy*; D005234:Fatty Liver / Q000150:complications / Q000628:therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease; D010805:Physical Conditioning, Animal; D051381:Rats; D020334:Rats, Inbred OLETF; D012420:Running / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Otsuka Long-Evans Tokushima Fatty rats; de novo lipogenesis; exercise training; hepatic mitochondria; metformin; nonalcoholic fatty liver disease