SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation.

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites, improving insulin sensitivity or promoting an immune-tolerant microenvironment that facilitates tumour growth and metastasis. Recently, the metabolic regulation of macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming.

Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of laminopathy.

LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of the pathology are unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) and a mouse model both harboring the p.

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells.

Objectives: Aging HIV-infected antiretroviral-treatment (ART)-controlled patients often present cardiovascular and metabolic comorbidities. Thus, it is mandatory that life-long used ART has no cardiometabolic toxicity. Protease inhibitors have been associated with cardiometabolic risk, integrase-strand-transfer-inhibitors (INSTI) with weight gain and the CCR5 inhibitor maraviroc with improved vascular function.

Brown and beige fat: From molecules to physiology and pathophysiology.

The adipose organ portrays adipocytes of diverse tones: white, brown and beige, each type with distinct functions. Adipocytes orchestrate their adaptation and expansion to provide storage to excess nutrients, the quick mobilisation of fuel to supply peripheral functional demands, insulation, and, in their thermogenic form, heat generation to maintain core body temperature. Thermogenic adipocytes could be targets for anti-obesity and anti-diabetic therapeutic approaches aiming to restore adipose tissue functionality and increase energy dissipation.

Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives.

Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and premature ageing syndromes. LMNA mutations have been shown to alter nuclear structure and stiffness, binding to partners at the nuclear envelope or within the nucleoplasm, gene expression and/or prelamin A maturation. LMNA-associated lipodystrophic features, combining generalized or partial fat atrophy and metabolic alterations associated with insulin resistance, could result from altered adipocyte differentiation or from altered fat structure.

The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks.

The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive.

'Basic and Applied Thermogenesis Research' Bridging the Gap.

Obesity is a major health problem without satisfactory pharmacological treatment. A promising strategy is to promote energy dissipation by activating brown/beige adipose tissue. However, for this strategy to succeed it requires improving the transferability amongst cellular, murine, and human systems and bridging the gap between basic and clinical research.

Functional Human Beige Adipocytes From Induced Pluripotent Stem Cells.

Activation of thermogenic beige adipocytes has recently emerged as a promising therapeutic target in obesity and diabetes. Relevant human models for beige adipocyte differentiation are essential to implement such therapeutic strategies. We report a straightforward and efficient protocol to generate functional human beige adipocytes from human induced pluripotent stem cells (hiPSCs).

A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.

Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching.

What the genetics of lipodystrophy can teach us about insulin resistance and diabetes.

Genetic lipodystrophic syndromes are rare diseases characterized by generalized or partial fat atrophy (lipoatrophy) associated with severe metabolic complications such as insulin resistance (IR), diabetes, dyslipidemia, nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last 15 years, mutations in several genes have been shown to be responsible for monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive transmission. Although the molecular basis of lipodystrophies is heterogeneous, most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or formation or maintenance of the adipocyte lipid droplet (LD), showing that primary alterations of adipose tissue (AT) can result in severe systemic metabolic and endocrine consequences.