Adipogenesis: A Necessary but Harmful Strategy.

Obesity is considered to significantly increase the risk of the development of a vast range of metabolic diseases. However, adipogenesis is a complex physiological process, necessary to sequester lipids effectively to avoid lipotoxicity in other tissues, like the liver, heart, muscle, essential for maintaining metabolic homeostasis and has a crucial role as a component of the innate immune system, far beyond than only being an inert mass of energy storage. In pathophysiological conditions, adipogenesis promotes a pro-inflammatory state, angiogenesis and the release of adipokines, which become dangerous to health. It results in a hypoxic state, causing oxidative stress and the synthesis and release of harmful free fatty acids. In this review, we try to explain the mechanisms occurring at the breaking point, at which adipogenesis leads to an uncontrolled lipotoxicity. This review highlights the types of adipose tissue and their functions, their way of storing lipids until a critical point, which is associated with hypoxia, inflammation, insulin resistance as well as lipodystrophy and adipogenesis modulation by Krüppel-like factors and miRNAs.

Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis.

Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on glucose metabolism, we presently analyzed the effect of biotin deprivation on glucose homeostasis and on pancreatic islet morphology. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-deficient or a biotin-control diet (0 or 7.2 µmol of free biotin/kg diet, respectively) over a period of 8 weeks. We found that biotin deprivation caused reduced concentrations of blood glucose and serum insulin concentrations, but increased plasma glucagon levels. Biotin-deficient mice also presented impaired glucose and insulin tolerance tests, indicating defects in insulin sensitivity. Altered insulin signaling was linked to a decrease in phosphorylated Akt/PKB but induced no change in insulin receptor abundance. Islet morphology studies revealed disruption of islet architecture due to biotin deficiency, and an increase in the number of α-cells in the islet core. Morphometric analyses found increased islet size, number of islets and glucagon-positive area, but a decreased insulin-positive area, in the biotin-deficient group. Glucagon secretion and gene expression increased in islets isolated from biotin-deficient mice. Our results suggest that biotin deficiency promotes hyperglycemic mechanisms such as increased glucagon concentration and decreased insulin secretion and sensitivity to compensate for reduced blood glucose concentrations. Variations in glucose homeostasis may participate in the changes observed in pancreatic islets.

Modulation of aortic vascular reactivity by sex hormones in a male rat model of metabolic syndrome.

Modulation by sex hormones of aortic reactivity in rats with the metabolic syndrome (MS) was investigated. The following groups of weanling male Wistar rats were used: control rats (C) received regular tap water while MS rats received 30% sucrose in their drinking water; both had rodent chow for 24 weeks. These two groups were further subdivided into the following four groups: intact (Int), castrated (Cas), castrated plus testosterone (T) and castrated plus estradiol (E). Vascular response of thoracic aortic rings to norepinephrine (NE), acetylcholine (ACh), indomethacin (Indo) and nitro-l-arginine-methyl ester (L-NAME) was investigated. Blood pressure (BP) and serum nitrates and nitrites were measured. BP and serum nitrates and nitrites were modified by castration and treatments with either T or E. Vasoconstriction in Int MS and Cas MS+T aortas was larger than in C and Cas C+T, respectively. Vasodilation in Int MS and Cas MS+T was reduced in comparison with C and Cas C+T, Cas MS and Cas MS+E. Indomethacin decreased vasoconstriction in all groups (P<0.002) but Int C and Cas C+T remained significantly smaller than Int MS and Cas MS+T. l-NAME in NE-contracted vessels induced a significant increase in vasoconstriction, except in Cas C+E rats; the responses of Int MS and Cas MS+T were significantly larger than in Int C and Cas C+T. The results suggest endothelial dysfunction in Int MS and Cas MS+T and a protective effect resulting from castration and castration plus E in MS animals, indicating a sex hormone influence.

Respiratory chain complexes and membrane fatty acids composition in rat testis mitochondria throughout development and ageing.

Throughout the maturation of germ cells, a morphological, biochemical and functional differentiation of mitochondria has been shown to occur. Ageing is known to cause changes involved in energy metabolism. These changes have been related to molecular and functional alterations in the properties of biological membranes. Variations in membrane lipid composition and lipid-protein interactions occur with ageing in several tissues. The present paper describes the relationship between these membrane alterations and the activities of lipid-dependent enzymes of isolated testis mitochondria in rats of from 10 days of age to 24 months. The specific activities of these enzymes are lower in preparations from adult and aged rats as compared to those from young rats. Temperature breaks of Arrhenius plots show age-dependent shifts to higher temperatures for the NADH-dehydrogenase, succinate-dehydrogenase, cytochrome c oxidase, and ATPase in senescent animals. Analysis of the membrane fatty acid composition reveals a distinct age-dependent fall in the content of polyunsaturated fatty acids accompanied by an increase in the proportion of saturated fatty acids and a decrease in polyunsaturated fatty acid percentage. The results suggest that during spermatogenesis and the ageing process some changes in the composition of the fatty acids in the surrounding membrane affect the protein-lipid interactions, producing a decrease in mitochondrial enzyme activities.