All Phenotypes C1qtnf12<tm1Gww> MGI Mouse

homeostasis/metabolism phenotype ( J:242627 )

N

• both male and female mice fed either an LFD or a HFD show no differences in VO2, VCO2, respiratory exchange ratio (VO2/ VCO2) and energy expenditure relative to sex- and diet-matched wild-type controls

• male mice fed either an LFD or a HFD show normal glucose tolerance, glucose-stimulated insulin secretion, insulin tolerance, or pyruvate tolerance relative to diet-matched wild-type males

• LFD-fed females show normal glucose tolerance, glucose-stimulated insulin secretion, insulin tolerance, and pyruvate tolerance relative to LFD-fed wild-type females

• after a 4 h fast, LFD-fed males show normal serum total cholesterol, triglyceride (TG), LDL-cholesterol, and HDL-cholesterol levels as well as normal liver TG and cholesterol content relative to LFD-fed wild-type males

• in a lipid tolerance test, LFD-fed males given an oral lipid gavage after an overnight fast show normal serum levels of TGs, non-esterified fatty acid (NEFA) and total cholesterol levels over the course of 4 h following oral lipid gavage; LFD-fed females also show normal lipid tolerance, as determined by serum TG levels

• after a 4 h fast, HFD-fed mice show normal serum total cholesterol, LDL-cholesterol, and HDL-cholesterol levels relative to HFD-fed wild-type controls

increased fatty acid oxidation ( J:242627 )

• after a 4 h fast, LFD-fed males show higher serum levels of beta-hydroxybutyrate than similarly fasted LFD-fed wild-type males

• LFD-fed males show increased mRNA expression of fatty oxidation genes (Cpt1a, Acadl/Lcad, and Ppara) in the liver

• however, LFD-fed males show normal mRNA expression of genes involved in lipid synthesis and uptake in the liver

• notably, HFD-fed males show normal mRNA levels of genes involved in oxidation, lipid synthesis, uptake and clearance in the liver as well as normal hepatic expression of pro-inflammatory genes

increased circulating ketone body level ( J:242627 )

• after a 4 h fast, LFD-fed males show higher serum levels of ketones (beta-hydroxybutyrate, a marker of hepatic fat oxidation) than similarly fasted LFD-fed wild-type males

• however, HFD-fed males show normal fasting serum ketone levels

decreased circulating free fatty acids level ( J:242627 )

• after an overnight (16 h) fast, LFD-fed males show lower serum non-esterified fatty acid (NEFA) levels than fasted LFD-fed wild-type males

• however, fasted HFD-fed males show normal NEFA levels

decreased circulating triglyceride level ( J:242627 )

• after a 4 h fast, HFD-fed males show lower serum TG levels than fasted HFD-fed wild-type males

• however, HFD-fed females show normal serum TG levels after a 4 h fast

decreased circulating VLDL triglyceride level ( J:242627 )

• LFD-fed males injected with Poloxamer 407 show lower serum TG levels at 4 h and 8 h post-injection than similarly treated LFD-fed wild-type males, with no change in serum cholesterol levels

• HFD-fed males injected with Poloxamer 407 show lower serum TG levels at 9 h post-injection, again with no change in serum cholesterol levels

increased circulating triglyceride level ( J:242627 )

• in a lipid tolerance test, HFD-fed males given an oral lipid gavage after an overnight fast show higher serum TG levels at the 2 h point but not later, indicating impaired clearance of postprandial lipids

• however, HFD-fed males show normal serum NEFA and total cholesterol levels in lipid tolerance tests

• moreover, HFD-fed females show normal serum TG and NEFA levels after acute lipid gavage in lipid tolerance tests

increased circulating VLDL triglyceride level ( J:242627 )

• unlike males, HFD-fed females injected with Poloxamer 407 show higher serum TG levels at 9 h post-injection, with no change in serum cholesterol levels

insulin resistance ( J:242627 )

• female mice fed a HFD for 12 weeks show reduced insulin sensitivity, as indicated by higher fasting insulin levels at 0 min post-glucose injection, as well as reduced glucose clearance, as indicated by higher blood glucose levels at 15 min after insulin injection in insulin tolerance tests

• HFD-fed females also show higher hepatic glucose output at 15 min after sodium pyruvate injection in a pyruvate tolerance test, consistent with mild insulin resistance

• however, HFD-fed females show normal glucose tolerance relative to HFD-fed wild-type females

increased liver cholesterol level ( J:242627 )

• HFD-fed males show elevated liver cholesterol levels relative to HFD-fed wild-type males

increased liver triglyceride level ( J:242627 )

• HFD-fed males show elevated liver TG levels relative to HFD-fed wild-type males

increased liver cholesterol level ( J:242627 )

• HFD-fed males show elevated liver cholesterol levels relative to HFD-fed wild-type males

increased liver triglyceride level ( J:242627 )

• HFD-fed males show elevated liver TG levels relative to HFD-fed wild-type males

increased susceptibility to diet-induced hepatic steatosis ( J:242627 )

• HFD-fed males exhibit greater steatosis with higher liver triglyceride and cholesterol levels than HFD-fed wild-type males

decreased liver triglyceride secretion ( J:242627 )

• LFD-fed males injected with Poloxamer 407 (an inhibitor of lipoprotein lipase activity) show decreased hepatic VLDL-triglyceride secretion relative to similarly treated LFD-fed wild-type males at 4 h and 8 h post-injection

• HFD-fed males injected with Poloxamer 407 show decreased hepatic VLDL-triglyceride secretion at 9 h post-injection relative to similarly treated HFD-fed wild-type males

• further, LFD-fed males show a modest increase in the mRNA expression of genes involved in VLDL clearance (Lipc and Apoe) in the liver; a combination of increased fatty oxidation and VLDL clearance may result in lower VLDL-TG export from the liver

• however, LFD-fed females show normal hepatic triglyceride secretion

increased liver triglyceride secretion ( J:242627 )

• unlike males, HFD-fed females injected with Poloxamer 407 show increased hepatic VLDL-triglyceride secretion at 9 h post-injection relative to HFD-fed females

growth/size/body region phenotype ( J:242627 )

N

• both male and female mice fed a control LFD show normal body weight gain over the course of 16 weeks relative to LFD-fed wild-type controls

• at 20 weeks of age, LFD-fed mice show no differences in organ (kidney and liver) weight, total lean and fat mass relative to LFD-fed wild-type controls

• similarly, mice fed a HFD for 12 weeks show normal body weight, body composition, and organ weight relative to HFD-fed wild-type controls

adipose tissue phenotype ( J:242627 )

N	• mice fed either an LFD or a HFD show normal epididymal white adipose tissue (eWAT, males) and inguinal WAT (iWAT, both sexes) weight relative to diet-matched wild-type controls

behavior/neurological phenotype ( J:242627 )

N	• mice fed either an LFD or a HFD show normal food intake and physical activity levels (as measured by infrared beam breaks in a metabolic chamber) relative to diet-matched wild-type controls

increased fatty acid oxidation ( J:242627 )

• after a 4 h fast, LFD-fed males show higher serum levels of beta-hydroxybutyrate than similarly fasted LFD-fed wild-type males

• LFD-fed males show increased mRNA expression of fatty oxidation genes (Cpt1a, Acadl/Lcad, and Ppara) in the liver

• however, LFD-fed males show normal mRNA expression of genes involved in lipid synthesis and uptake in the liver

• notably, HFD-fed males show normal mRNA levels of genes involved in oxidation, lipid synthesis, uptake and clearance in the liver as well as normal hepatic expression of pro-inflammatory genes

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

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