期刊
JOURNAL OF LIPID RESEARCH
卷 55, 期 7, 页码 1434-1447出版社
ELSEVIER
DOI: 10.1194/jlr.M050047
关键词
testosterone; metabolic syndrome; low density lipoprotein receptor-related protein 1; apolipoprotein E; diabetes; plasma glucose homeostasis; metabolic rate; uncoupling protein 1; metabolic activation of white adipose tissue
资金
- European Social Fund
- Greek state
- MRC [MC_UU_12012/5] Funding Source: UKRI
- Medical Research Council [MC_UU_12012/5, MC_UU_12012/5/B] Funding Source: researchfish
Here, we investigated how LDL receptor defi ciency (Ldlr(-/-)) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr(-/-) mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr(-/-) mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr(-/-) mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr(-/-) mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr(-/-) mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr(-/-) mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism.
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