All Phenotypes Mc4r<tm1Matsu> MGI Mouse

growth/size/body

increased susceptibility to diet-induced obesity ( J:285412 )

• body weight of mice fed a Western diet is 1.8x greater than that of lean control mice

• mutant mice fed a Western diet treated with GS-0976, a liver-targeted inhibitor of ACC1/2, show suppressed weight gain, without affecting food intake

increased liver weight ( J:285412 )

• liver weights are 4.3-fold higher than in lean control mice on a Western diet

behavior/neurological

increased food intake ( J:285412 )

• cumulative caloric intake of mutant mice is 1.5 times higher compared to control mice on a Western diet

liver/biliary system

increased liver weight ( J:285412 )

• liver weights are 4.3-fold higher than in lean control mice on a Western diet

increased liver triglyceride level ( J:285412 )

• hepatic triglyceride content is 12-fold higher than in lean control mice on a Western diet

• however, plasma triglyceride concentrations in Western diet-fed mice are similar to lean controls

liver inflammation ( J:285412 )

• weak lobular inflammation is seen in Western diet-fed mice

• mice show increased hepatic gene expression related to inflammation

hepatic steatosis ( J:285412 )

• Western diet-fed mice show increased hepatic steatosis

• GS-0976 treatment lowers steatosis

liver fibrosis ( J:285412 )

• hepatic fibrosis is exacerbated during 9 weeks of Western diet feeding

• mice show increased hepatic gene expression related to fibrosis

• GS-0976 treatment suppresses the progression of fibrosis

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:285412 )

• body weight of mice fed a Western diet is 1.8x greater than that of lean control mice

• mutant mice fed a Western diet treated with GS-0976, a liver-targeted inhibitor of ACC1/2, show suppressed weight gain, without affecting food intake

increased hydroxyproline level ( J:285412 )

• hepatic hydroxyproline content is 1.9-fold increased after 9 weeks of Western diet feeding

• GS-0976 treatment lowers hydroxyproline content

increased circulating insulin level ( J:285412 )

• mice fed a Western diet develop hyperinsulinemia, although they maintain normoglycemia

• treatment with GS-0976 increases plasma insulin concentrations

increased circulating cholesterol level ( J:285412 )

• total cholesterol concentrations are 4x higher than in controls when fed a Western diet

• treatment with GS-0976 lowers plasma total cholesterol levels

increased circulating alanine transaminase level ( J:285412 )

• mice fed a Western diet show higher plasma ALT levels

• treatment with GS-0976 lowers plasma ALT levels

increased circulating aspartate transaminase level ( J:285412 )

• mice fed a Western diet show higher AST levels

• treatment with GS-0976 lowers plasma AST levels