Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet.
The aims of this study were designed to determine whether liraglutide, a long-acting glucagon-like peptide, could reverse the adverse effects of a diet high in fat that also contained trans-fat and high-fructose corn syrup (ALIOS diet). Specifically, we examined whether treatment with liraglutide could reduce hepatic insulin resistance and steatosis as well as improve cardiac function. Male C57BL/6J mice were pair fed or fed ad libitum either standard chow or the ALIOS diet. After 8 wk the mice were further subdivided and received daily injections of either liraglutide or saline for 4 wk. Hyperinsulinemic-euglycemic clamp studies were performed after 6 wk, revealing hepatic insulin resistance. Glucose tolerance and insulin resistance tests were performed at 8 and 12 wk prior to and following liraglutide treatment. Liver pathology, cardiac measurements, blood chemistry, and RNA and protein analyses were performed. Clamp studies revealed hepatic insulin resistance after 6 wk of ALIOS diet. Liraglutide reduced visceral adiposity and liver weight (P < 0.001). As expected, liraglutide improved glucose and insulin tolerance. Liraglutide improved hypertension (P < 0.05) and reduced cardiac hypertrophy. Surprisingly, liver from liraglutide-treated mice had significantly higher levels of fatty acid binding protein, acyl-CoA oxidase II, very long-chain acyl-CoA dehydrogenase, and microsomal triglyceride transfer protein. We conclude that liraglutide reduces the harmful effects of an ALIOS diet by improving insulin sensitivity and by reducing lipid accumulation in liver through multiple mechanisms including, transport, and increase β-oxidation.
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta GA 30322, USA.
Jamie E
JE
Mells
Ping P
PP
Fu
Shvetank
S
Sharma
Darin
D
Olson
Lihong
L
Cheng
Jeffrey A
JA
Handy
Neeraj K
NK
Saxena
Dan
D
Sorescu
Frank A
FA
Anania
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007333:Insulin Resistance; D000069450:Liraglutide; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1