Pex11a deficiency causes dyslipidaemia and obesity in mice.
Peroxisomes play a central role in lipid metabolism. We previously demonstrated that Pex11a deficiency impairs peroxisome abundance and fatty acid β-oxidation and results in hepatic triglyceride accumulation. The role of Pex11a in dyslipidaemia and obesity is investigated here with Pex11a knockout mice (Pex11a-/- ). Metabolic phenotypes including tissue weight, glucose tolerance, insulin sensitivity, cholesterol levels, fatty acid profile, oxygen consumption, physical activity were assessed in wild-type (WT) and Pex11a-/- fed with a high-fat diet. Molecular changes and peroxisome abundance in adipose tissue were evaluated through qRT-PCR, Western blotting, and Immunofluorescence. Pex11a-/- showed increased fat mass, decreased skeletal muscle, higher cholesterol levels, and more severely impaired glucose and insulin tolerance. Pex11a-/- consumed less oxygen, indicating a decrease in fatty acid oxidation, which is consistent with the accumulation of very long- and long-chain fatty acids. Adipose palmitic acid (C16:0) levels were elevated in Pex11a-/- , which may be because of dramatically increased fatty acid synthase mRNA and protein levels. Furthermore, Pex11a deficiency increased ventricle size and macrophage infiltration, which are related to the reduced physical activity. These data demonstrate that Pex11a deficiency impairs physical activity and energy expenditure, decreases fatty acid β-oxidation, increases de novo lipogenesis and results in dyslipidaemia and obesity.
['Chen|Congcong|C|', 'Wang|Hongwei|H|', 'Chen|Bicheng|B|', 'Chen|Deyuan|D|', 'Lu|Chaosheng|C|', 'Li|Haiyan|H|', 'Qian|Yan|Y|', 'Tan|Yi|Y|', 'Weng|Huachun|H|0000-0002-7446-6001', 'Cai|Lu|L|']
D000273:Adipose Tissue D000818:Animals D002784:Cholesterol D059305:Diet, High-Fat D050171:Dyslipidemias D004734:Energy Metabolism D005227:Fatty Acids D007333:Insulin Resistance D050356:Lipid Metabolism D050155:Lipogenesis D008066:Lipolysis D008099:Liver D008565:Membrane Proteins D051379:Mice D018345:Mice, Knockout D009765:Obesity D020675:Peroxisomes D014280:Triglycerides
obesity peroxisomes adipose tissue lipogenesis fatty acid metabolism