All Phenotypes Pon3<tm1Dmsh> MGI Mouse

mortality/aging ( J:234615 )

N	• mice are born in normal Mendelian ratios and remain viable as adults, unlike Pon3^tm1Tigm homozygotes

increased susceptibility to induced morbidity/mortality ( J:234615 )

• when fed a cholate-cholesterol (CC) diet for 16 weeks, only 65% of CC-fed mice survive versus 96% of wild-type controls likely due to cholestasis caused by increased gallstone formation

increased body weight ( J:234615 )

• when fed a Western diet for 10 weeks, mice show a 37% increase in body weight

• however, daily food consumption is normal

increased susceptibility to diet-induced obesity ( J:234615 )

• mice show increased obesity following a Western diet for 10 weeks

increased susceptibility to atherosclerosis ( J:234615 )

• when fed a cholate-cholesterol (CC) diet for 16 weeks, mice show a 60% increase in mean atherosclerotic lesion size at the aortic root region relative to wild-type controls; only 65% of CC-fed mice survive versus 96% of CC-fed wild-type controls

decreased fatty acid oxidation ( J:234615 )

• following a Western diet for 10 weeks, mice show decreased oxygen consumption rate (OCR) in gonadal and subcutaneous fat pads in response to palmitate treatment

increased susceptibility to diet-induced obesity ( J:234615 )

• mice show increased obesity following a Western diet for 10 weeks

increased circulating bilirubin level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a dramatic increase in plasma direct bilirubin levels, consistent with increased hepatoxicity

decreased oxygen consumption ( J:234615 )

• in the presence of succinate and rotenone, liver mitochondria from chow-fed mice show a significantly lower OCR in response to ADP (state 3) and FCCP (state 3u), indicating reduced mitochondrial respiration

• following a Western diet for 10 weeks, mice show decreased OCR in gonadal and subcutaneous fat pads in response to FCCP (uncoupler) or palmitate treatment

• OCR of differentiated white adipocytes derived from mice fed a Western diet is substantially decreased in response to FCCP, but not in response to oligomycin or rotenone/myxotiazol treatment

abnormal bile salt homeostasis ( J:234615 )

• when fed a CC diet for 16 weeks, mice show altered hepatic expression of several genes involved in bile acid metabolism indicating decreased hepatic bile acid synthesis

abnormal lipid level ( J:234615 )

• when fed a CC diet for 10 weeks (to avoid mortality), mice show increased phosphatidate levels in the liver

decreased circulating HDL cholesterol level ( J:234615 )

• when fed a CC diet for 10 weeks (to avoid mortality), mice show a significant decrease in plasma HDL cholesterol levels

increased circulating cholesterol level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show significant increases in plasma total cholesterol (320%), very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL cholesterol (466%), and unesterified cholesterol (896%) levels

• when fed a CC diet for 10 weeks (to avoid mortality), mice show significant increases in plasma total and VLDL/IDL/LDL cholesterol levels

increased circulating LDL cholesterol level ( J:234615 )

• when fed a CC diet for 10 weeks, mice show increased plasma IDL/LDL levels

decreased circulating free fatty acids level ( J:234615 )

• on a chow diet, mice show a small but significant decrease in plasma free fatty acid levels

decreased circulating triglyceride level ( J:234615 )

• on a chow diet, mice show a small but significant decrease in plasma triglyceride levels

increased circulating triglyceride level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a 267% increase in plasma triglyceride levels

decreased bile salt level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show significantly decreased levels of endogenously synthesized bile acids, muricholic acid (MCA), chenodeoxycholic acid (CDCA), and ursodeoxycholic acid (UDCA) in the small intestine

increased bile salt level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a 273% increase in plasma bile acid levels; when fed a CC diet for 10 weeks (to avoid mortality), mice show significantly increased plasma total bile acid levels

• when fed a Western diet, mice show significantly elevated plasma total bile acid levels

• however, no differences in plasma total bile acids are noted on a chow diet

increased liver cholesterol level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show significant increases in liver total cholesterol (40%), cholesterol ester (44%), and unesterified cholesterol (22%) levels

decreased liver triglyceride level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a 56% decrease in liver triglyceride levels

• when fed a CC diet for 10 weeks, mice show reduced expression of lipogenic genes and decreased triglyceride and diacylglycerol levels in the liver

abnormal protein level ( J:234615 )

• when fed a CC diet for 10 weeks, mice show increased lipin 2 (LPIN2) protein levels in the liver

• however, liver phosphatidic acid phosphatase (PAP) activity is normal

increased circulating alanine transaminase level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a dramatic increase in plasma alanine aminotransferase levels, consistent with increased hepatoxicity

increased circulating aspartate transaminase level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a dramatic increase in plasma aspartate aminotransferase levels, consistent with increased hepatoxicity

increased hepatocyte apoptosis ( J:234615 )

• following a CC diet for 10 weeks, mice show a 66% increase in TUNEL+ cells in the liver

increased liver cholesterol level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show significant increases in liver total cholesterol (40%), cholesterol ester (44%), and unesterified cholesterol (22%) levels

decreased liver triglyceride level ( J:234615 )

• when fed a CC diet for 16 weeks, mice show a 56% decrease in liver triglyceride levels

• when fed a CC diet for 10 weeks, mice show reduced expression of lipogenic genes and decreased triglyceride and diacylglycerol levels in the liver

liver inflammation ( J:234615 )

• when fed a CC diet for 16 weeks, mice show increased hepatic expression of inflammatory genes

• however, no evidence of liver pathology is observed on a chow diet

gallstones ( J:234615 )

• when fed a CC diet for 10 weeks, mice show increased gallstone formation with a 58% increase in gallstone weight

• gallstone formation is likely due to decreased bile acid secretion and increased cholesterol excretion into bile

abnormal bile composition ( J:234615 )

• when fed a CC diet for 10 weeks, mice show increased cholesterol and phospholipid levels in the gallbladder bile and a 39% increase in cholesterol levels in hepatic bile samples

• following a CC diet for 16 weeks, all bile acid species are significantly increased in plasma; in the liver, total bile acid content is normal whereas levels of several unconjugated bile acids are significantly decreased; bile samples show a significant decrease in deoxycholic acid levels and a trend towards decreased levels of other bile acids

jaundice ( J:234615 )

• following a CC diet for 16 weeks, critically ill mice exhibit jaundice

increased subcutaneous adipose tissue amount ( J:234615 )

• following a Western diet for 10 weeks, subcutaneous fat pad weight is significantly increased

increased white fat cell lipid droplet size ( J:234615 )

• stromal vascular cells isolated from the subcutaneous fat pads of mice fed a Western diet and differentiated in vitro exhibit a white adipocyte phenotype with large lipid droplet-filled cells

increased white fat cell size ( J:234615 )

• following a Western diet for 10 weeks, average size of adipocytes of the gonadal fat pad is increased by 25%

increased gonadal fat pad weight ( J:234615 )

• following a Western diet for 10 weeks

increased retroperitoneal fat pad weight ( J:234615 )

• following a Western diet for 10 weeks

increased hepatocyte apoptosis ( J:234615 )

• following a CC diet for 10 weeks, mice show a 66% increase in TUNEL+ cells in the liver

abnormal mitochondrial ATP synthesis coupled electron transport ( J:234615 )

• in the presence of succinate and rotenone, liver mitochondria from chow-fed mice show a significantly lower OCR in response to ADP (state 3) and FCCP (state 3u), indicating reduced complex II-IV-dependent mitochondrial respiration

• following a CC diet for 10 weeks, liver mitochondria show significantly decreased complex II + III activity