Bovine growth hormone transgenic mice are resistant to diet-induced obesity but develop hyperphagia, dyslipidemia, and diabetes on a high-fat diet.
It is known that bovine GH (bGH) transgenic mice have increased body mass, insulin resistance, and altered lipoprotein metabolism when fed a normal diet (ND). In this study, the effects of 8 wk of high-fat diet (HFD) were investigated in 6-month-old male bGH mice. Although littermate controls had unchanged energy intake, energy intake was higher in the bGH mice on a HFD than on a low-fat diet. Nevertheless, the bGH mice were resistant to diet-induced weight gain, and only in the bGH mice did the HFD result in increased energy expenditure. Glucose oxidation was higher in the bGH mice compared with littermate controls on both a HFD and ND. In addition, the bGH mice had 0.5 C higher body temperature throughout the day and increased hepatic uncoupling protein 2 expression; changes that were unaffected by the HFD. On a HFD, the effect of bGH overexpression on serum triglycerides and apolipoprotein B was opposite to that on a ND, resulting in higher serum concentrations of triglycerides and apolipoprotein B compared with littermate controls. Increased serum triglycerides were explained by decreased triglyceride clearance. The HFD led to diabetes only in the bGH mice. In conclusion, bGH transgenic mice were resistant to diet-induced obesity despite hyperphagia, possibly due to increased energy expenditure. On a HFD, bGH mice became dyslipidemic and diabetic and thereby more accurately reflect the metabolic situation in acromegalic patients.
Olsson
Bob
B
Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Vita Stråket 12, S-413 45 Göteborg, Sweden. bob.olsson@medic.gu.se
Bohlooly-Y
Mohammad
M
Fitzgerald
Sharyn M
SM
Frick
Fredrik
F
Ljungberg
Anna
A
Ahrén
Bo
B
Törnell
Jan
J
Bergström
Göran
G
Oscarsson
Jan
J
D000172:Acromegaly / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001823:Body Composition; D001831:Body Temperature; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004041:Dietary Fats / Q000494:pharmacology; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000235:genetics*; D006949:Hyperlipidemias / Q000378:metabolism / Q000503:physiopathology*; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology*; D007473:Ion Channels; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000502:physiology; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
D002352:Carrier Proteins; D004041:Dietary Fats; D007473:Ion Channels; D008055:Lipids; D008074:Lipoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D013006:Growth Hormone