No abstract

Metabolic syndrome (MetS) is a complex, emerging epidemic which disrupts the metabolic homeostasis of several organs, including liver, heart, pancreas, and adipose tissue. While studies have been conducted in these research areas, the pathogenesis and mechanisms of MetS remain debatable. Lines of evidence show that physiological systems, such as the renin-angiotensin system (RAS) and autophagy play vital regulatory roles in MetS. RAS is a pivotal system known for controlling blood pressure and fluid balance, whereas autophagy is involved in the degradation and recycling of cellular components, including proteins. Although RAS is activated in MetS, the interrelationship between RAS and autophagy varies in glucose homeostatic organs and their cross talk is poorly understood. Interestingly, autophagy is attenuated in the liver during MetS, whereas autophagic activity is induced in adipose tissue during MetS, indicating tissue-specific discordant roles. We discuss in vivo and in vitro studies conducted in metabolic tissues and dissect their tissue-specific effects. Moreover, our review will focus on the molecular mechanisms by which autophagy orchestrates MetS and the ways future treatments could target RAS in order to achieve metabolic homeostasis. Facts • The renin-angiotensin system (RAS) is a pivotal endocrine system classically known for controlling blood pressure and fluid balance.

Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8+ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8+ T cells at the expense of CD4+ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8+ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells.

Insulin is a pivotal regulator of glucose metabolism and exerts an important anabolic function throughout the body. Insulin commands the glucose uptake by the cells and might control the processes in which there is need for energy such as mitogenesis and gene transcription. In certain conditions, diabetes mellitus for example, when insulin is diminished, the homeostasis of many tissues and organs are broken what can lead to a higher mortality due to an enhanced susceptibility to infections. This vulnerability to infections can partially be explained by a change in response to inflammation. In fact, diabetic animals and patients show a deficient inflammatory response. Many animal models have shown that neutrophils chemotaxis and recruitment are dampened and macrophages from diabetic patients have low phagocytic and microbicidal activities. In most cases, once insulin therapy is introduced, clinical symptoms and signs can be reverted. In addition, there are a number of studies trying to demystify pathways under insulin command. Researchers are also trying to understand how insulin is able to keep inflammatory response under control, restores innate immune cells ability to fight against pathogens and harmlessly activates adaptive immunity response. This review provides an overview on how inflammatory response is driven in the absence of insulin in diabetes and discusses recent findings on the influence of insulin on innate imune response. At the end, some signaling pathways are also highlighted and important enzymes and proteins that control DNA transcription are presented.