| First Author | Constantinou C | Year | 2014 |
| Journal | J Lipid Res | Volume | 55 |
| Issue | 7 | Pages | 1434-47 |
| PubMed ID | 24837748 | Mgi Jnum | J:215003 |
| Mgi Id | MGI:5604341 | Doi | 10.1194/jlr.M050047 |
| Citation | Constantinou C, et al. (2014) The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations. J Lipid Res 55(7):1434-1447 |
| abstractText | Here, we investigated how LDL receptor deficiency (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. |
