RESUMEN
AIMS: Although anabolic steroids (AS) and trans-fatty acids overload exerts systemic toxicity and are independent risk factors for metabolic and cardiovascular disorders, their interaction remains poorly understood. Thus, we investigated the impact of a diet rich in trans-fatty acids (HFD) combined with AS on glycemic control, lipid profile, adipose tissue, skeletal muscle and pancreas microstructure and expression of genes involved in energy metabolism. MAIN METHODS: Forty-eight C57BL/6 mice were randomized into 6 groups treated for 12â¯weeks with a standard diet (SD) or a diet rich in C18:1 trans-fatty isomers (HFD), alone or combined with 10 or 20â¯mg/kg testosterone cypionate (AS). KEY FINDINGS: Our results indicated that AS improved glycemic control, upregulated gene expression of Glut-4 and CPT-1 in skeletal muscle, FAS, ACC and UCP-1 in adipose tissue. AS also reduced total and LDL cholesterol in mice fed a SD. When combined with the HFD, AS was unable to induce microstructural adaptations in adipose tissue, pancreatic islets and ß-cells, but potentiated GCK and Glut-2 (pancreas) and Glut-4 and CPT-1 (skeletal muscle) upregulation. HFD plus AS also downregulated FAS and ACC gene expression in adipose tissue. Combined with HFD, AS increased triacylglycerol circulating levels, improved insulin sensitivity and glycemic control in mice. SIGNIFICANCE: Our findings indicated that HFD and AS can interact to modulates glycemic control and lipid profile by a mechanism potentially related with a reprogramming of genes expression in organs such as the pancreas, adipose tissue and skeletal muscle.
Asunto(s)
Congéneres de la Testosterona/genética , Congéneres de la Testosterona/metabolismo , Ácidos Grasos trans/metabolismo , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/fisiología , Femenino , Glucosa/metabolismo , Carga Glucémica/fisiología , Resistencia a la Insulina/genética , Metabolismo de los Lípidos/fisiología , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Páncreas/metabolismo , Ácidos Grasos trans/fisiologíaRESUMEN
Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). ß-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that ßecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that ßecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of ßecdysterone on IDD was explored by in vitro experiments. The results demonstrated that ßecdysterone attenuated the apoptosis induced by tertbutyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by ßecdysterone in a dose and timedependent manner in nucleus pulposus cells. Inhibition of autophagy with 3methyladenine partially abrogated the protective function of ßecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of ßecdysterone on IDD. Additionally, ßecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that ßecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that ßecdysterone may be a potential therapeutic agent for IDD.
Asunto(s)
Autofagia/efectos de los fármacos , Proteína Receptora de AMP Cíclico/administración & dosificación , Ecdisterona/administración & dosificación , Degeneración del Disco Intervertebral/tratamiento farmacológico , Núcleo Pulposo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Beclina-1/genética , Ecdisterona/genética , Humanos , Disco Intervertebral/efectos de los fármacos , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/fisiopatología , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Osteoblastos/efectos de los fármacos , Sustancias Protectoras/administración & dosificación , Ratas , Congéneres de la Testosterona/biosíntesis , Congéneres de la Testosterona/genéticaRESUMEN
Insulin is the paramount anabolic hormone, promoting carbon energy deposition in the body. Its synthesis, quality control, delivery, and action are exquisitely regulated by highly orchestrated intracellular mechanisms in different organs or "stations" of its bodily journey. In this Beyond the Cell review, we focus on these five stages of the journey of insulin through the body and the captivating cell biology that underlies the interaction of insulin with each organ. We first analyze insulin's biosynthesis in and export from the ß-cells of the pancreas. Next, we focus on its first pass and partial clearance in the liver with its temporality and periodicity linked to secretion. Continuing the journey, we briefly describe insulin's action on the blood vasculature and its still-debated mechanisms of exit from the capillary beds. Once in the parenchymal interstitium of muscle and adipose tissue, insulin promotes glucose uptake into myofibers and adipocytes, and we elaborate on the intricate signaling and vesicle traffic mechanisms that underlie this fundamental function. Finally, we touch upon the renal degradation of insulin to end its action. Cellular discernment of insulin's availability and action should prove critical to understanding its pivotal physiological functions and how their failure leads to diabetes.
Asunto(s)
Resistencia a la Insulina/genética , Insulina/metabolismo , Congéneres de la Testosterona/metabolismo , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Glucosa/metabolismo , Humanos , Insulina/biosíntesis , Insulina/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Congéneres de la Testosterona/biosíntesis , Congéneres de la Testosterona/genéticaRESUMEN
BACKGROUND: Despite decades of research, the genetic basis of coronary heart disease and its metabolic risk factors is poorly understood. Few studies consider that sex may modify the effect of gene variants on disease. Investigation of gene by sex interaction may help to elucidate underlying genetic susceptibilities and explain the sexual dimorphism of these complex traits. AIMS: The aim of this review is to summarize evidence for gene by sex interaction in the etiology of coronary heart disease and the metabolic syndrome. DATA SYNTHESIS: Published literature was examined in the areas of familial aggregation of coronary heart disease; heritability of body mass, insulin resistance, hypertension and dyslipidemia; genome-wide linkage analysis in humans and rodents; and large-scale genetic association studies. Possible mechanisms of gene by sex interaction are discussed including X-linked inheritance, confounding by risk factors and the effect of sex hormones. CONCLUSIONS: The strongest evidence for gene by sex interaction in relation to coronary heart disease and the metabolic syndrome is in the etiology of body mass, insulin resistance and possibly dyslipidemia. Genetic studies of these traits would benefit from taking sex differences into account. Alternative mechanisms underlying gene by sex interaction, besides obvious sex hormone differences, should be considered.