All Phenotypes Serpina3c<em1Smoc> MGI Mouse

increased circulating triglyceride level ( J:343846 )

• after 16 weeks of high-fat diet (HFD) feeding, male mice exhibit significantly higher serum triglyceride levels than HFD-fed wild-type controls

• however, no differences in serum total cholesterol, LDL or HDL levels are observed

decreased energy expenditure ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit reduced energy expenditure relative to HFD-fed wild-type controls

increased susceptibility to diet-induced obesity ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly higher diet-induced body weight gain, fat mass amount, inguinal white adipose tissue (iWAT) and epididymal WAT (eWAT) weight than HFD-fed wild-type controls

• however, food intake (g/day) is relatively normal under HFD conditions, and no overt abnormalities are seen under normal chow diet (NCD) feeding

decreased carbon dioxide production ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly lower carbon dioxide production rate (VCO2) during a light/dark cycle than HFD-fed wild-type controls

decreased oxygen consumption ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly lower whole-body oxygen consumption rate (VO2) during a light/dark cycle than HFD-fed wild-type controls

• ex vivo, oxygen consumption rates in iWAT, eWAT, brown adipose tissue (BAT) and liver are consistently lower than in HFD-fed wild-type controls

impaired glucose tolerance ( J:343846 )

• HFD-fed male mice exhibit more severe glucose intolerance than HFD-fed wild-type controls

insulin resistance ( J:343846 )

• however, serum insulin levels are normal under basal conditions

• HFD-fed male mice exhibit more severe insulin resistance than HFD-fed wild-type controls

abnormal protein level ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit decreased protein levels of alpha5 and beta1 Integrin in iWAT

• however, mRNA expression of integrin alpha5 and integrin beta1 is relatively normal under HFD conditions

abnormal enzyme/coenzyme activity ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly higher cathepsin G activity in serum and in iWAT and eWAT than HFD-fed wild-type controls

• however, mRNA expression of Ctsg (cathepsin G) is relatively normal under HFD conditions

increased white fat cell size ( J:343846 )

• HFD-fed male mice exhibit significantly larger lipid droplets in iWAT and eWAT than HFD-fed wild-type controls, indicating white adipocyte hypertrophy

increased epididymal fat pad weight ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly higher eWAT weight than HFD-fed wild-type controls

increased inguinal fat pad weight ( J:343846 )

• after 16 weeks of HFD feeding, male mice exhibit a significantly higher iWAT weight than HFD-fed wild-type controls

decreased adipocyte glucose uptake ( J:343846 )

• HFD-fed male mice exhibit a significantly lower basal and insulin-stimulated 2-deoxyglucose (2-DG) uptake in iWAT and eWAT than HFD-fed wild-type controls, indicating aggravated insulin resistance in white adipose tissue

• only slight changes, but with similar trends, are observed in 2-DG uptake in BAT, liver, and muscle

abnormal white adipose tissue physiology ( J:343846 )

• HFD-fed male mice show enhanced JNK phosphorylation as well as attenuated basal and insulin-induced AKT phosphorylation in iWAT and eWAT, with no significant differences in JNK activation seen in BAT, liver and muscle

increased white adipose tissue apoptosis ( J:343846 )

• HFD-fed male mice show a marked increase in caspase-3 activity in iWAT and eWAT, indicating increased cell apoptosis in white adipose tissue

white adipose tissue inflammation ( J:343846 )

• HFD-fed male mice exhibit a significant increase in mRNA expression of inflammatory genes, including Nlrp3, Tnf, Il1b, Il6, Il18 and Ccl2 (aka Mcp1), in iWAT and eWAT, indicating adipose tissue inflammation

• under HFD conditions, aggravated adipose inflammation is at least in part due to reduced AKT signaling and enhanced JNK activity