RESUMO
The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass. By genome-wide expression analysis using hypothalamus RNA from wild-type and ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction. Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels. Although all of these parameters were identical to wild-type controls in Ttr-deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly, all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age. Taken together, our data demonstrate that the increased expression of Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.
Assuntos
Hipotálamo/metabolismo , Leptina/metabolismo , Obesidade/metabolismo , Fenótipo , Pré-Albumina/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal , Osso e Ossos/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Insulina/sangue , Resistência à Insulina , Leptina/genética , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Mutação , Obesidade/genética , Pré-Albumina/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
AIMS/HYPOTHESIS: Apolipoprotein E (ApoE) deficiency is associated with reduced fat accumulation in white adipose tissue (WAT) and high liver triacylglycerol content. Elevated levels of endocannabinoids and cannabinoid receptor type 1 (CB(1)) receptors in the liver and in epididymal vs subcutaneous WAT are associated with fatty liver, visceral adipose tissue, inflammatory markers and insulin resistance. METHODS: We investigated, in Apoe (-/-) and wild-type (WT) mice, the effect of a high-fat diet (HFD) on: (1) subcutaneous and epididymal WAT accumulation, liver triacylglycerols, phospholipid-esterified fatty acids, inflammatory markers in WAT and liver, and insulin resistance; and (2) endocannabinoid levels, and the gene expression levels of the Cb ( 1 ) receptor and endocannabinoid metabolic enzymes in liver and WAT. RESULTS: After a 16 week HFD, Apoe (-/-) mice exhibited lower body weight, WAT accumulation and fasting leptin, glucose and insulin levels, and higher hepatic steatosis, than WT mice. Glucose clearance and insulin-mediated glucose disposal following the HFD were slower in WT than Apoe (-/-) mice, which exhibited higher levels of mRNA encoding inflammatory markers (tumour necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], cluster of differentiation 68 [CD68] and EGF-like module-containing mucin-like hormone receptor-like 1 [EMR1]) in the liver, but lower levels in epididymal WAT. HFD-induced elevation of endocannabinoid levels in the liver or epididymal WAT was higher or lower, respectively, in Apoe (-/-) mice, whereas HFD-induced decrease of subcutaneous WAT endocannabinoid and CB(1) receptor levels was significantly less marked. Alterations in endocannabinoid levels reflected changes in endocannabinoid catabolic enzymes in WAT, or the availability of phospholipid precursors in the liver. CONCLUSIONS/INTERPRETATION: Liver and adipose tissue endocannabinoid tone following an HFD is altered on Apoe deletion and strongly associated with inflammation, insulin resistance and hepatic steatosis, or lack thereof.
Assuntos
Apolipoproteínas E/fisiologia , Moduladores de Receptores de Canabinoides/metabolismo , Gorduras na Dieta/efeitos adversos , Endocanabinoides , Fígado Gorduroso/metabolismo , Resistência à Insulina , Receptor CB1 de Canabinoide/metabolismo , Transdução de Sinais , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Animais , Apolipoproteínas E/genética , Células Cultivadas , Fígado Gorduroso/imunologia , Fígado Gorduroso/patologia , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Paniculite/imunologia , Paniculite/metabolismo , RNA Mensageiro/metabolismo , Receptor CB1 de Canabinoide/genética , Gordura Subcutânea/imunologia , Gordura Subcutânea/metabolismoRESUMO
The demagnetization dynamics of the Heusler alloy Co(2)MnSi was studied using picosecond time-resolved x-ray magnetic circular dichroism. The sample was excited using femtosecond laser pulses. In contrast to the sub-picosecond demagnetization of the metal ferromagnet Ni, substantially slower demagnetization with a time constant of 3.5 ± 0.5 ps was measured. This could be explained by a spin-dependent band gap inhibiting the spin-flip scattering of hot electrons in Co(2)MnSi, which is predicted to be half-metallic. A universal demagnetization time constant was measured across a range of pump power levels.
