Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity, but the molecular mechanisms that drive BAT cell remodeling remain largely unexplored. Using a multilayered approach, we comprehensively mapped a reorganization in BAT cells. We uncovered a subset of macrophages as lipid-associated macrophages (LAMs), which were massively increased in genetic and dietary model of BAT expansion.
View Article and Find Full Text PDFBrown adipose tissue (BAT) is mitochondria rich, enabling high oxidative metabolism for non-shivering thermogenesis. The release of large/small extracellular vesicles (EVs) containing mitochondria or mitochondrial fragments, termed mito-EVs, may support mitochondrial quality control or intercellular communication. We present a protocol to isolate and characterize mito-EVs.
View Article and Find Full Text PDFTrends Endocrinol Metab
November 2024
Intracellular metabolism is a crucial regulator of macrophage function. Recent evidence revealed that the polyamine pathway and subsequent hypusination of eukaryotic initiation factor 5A (eIF5A) are master regulators of immune cell functions. In brown adipose tissue (BAT), macrophages show an impressive degree of heterogenicity, with specific subsets supporting adaptive thermogenesis during cold exposure.
View Article and Find Full Text PDFImmunometabolism investigates the intricate relationship between the immune system and cellular metabolism. This study delves into the consequences of mitochondrial frataxin (FXN) depletion, the primary cause of Friedreich's ataxia (FRDA), a debilitating neurodegenerative condition characterized by impaired coordination and muscle control. By using single-cell RNA sequencing, we have identified distinct cellular clusters within the cerebellum of an FRDA mouse model, emphasizing a significant loss in the homeostatic response of microglial cells lacking FXN.
View Article and Find Full Text PDFThis study aims to obtain a cyto-compatible 3D printable bio-resin for the manufacturing of meshes designed from acquired real patients' bone defect to be used in future for guided bone regeneration (GBR), achieving the goal of personalized medicine, decreasing surgical, recovery time, and patient discomfort. To this purpose, a biobased, biocompatible, and photo-curable resin made of acrylated epoxidized soybean oil (AESO) diluted with soybean oil (SO) is developed and 3D printed using a commercial digital light processing (DLP) 3D printer. 3D printed samples show good thermal properties, allowing for thermally-based sterilization process and mechanical properties typical of crosslinked natural oils (i.
View Article and Find Full Text PDFFriedreich's ataxia (FA) is a neurodegenerative disease resulting from a mutation in the gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications.
View Article and Find Full Text PDFObjective: Accumulating evidence suggests that dysfunctional adipose tissue (AT) plays a major role in the risk of developing multiple sclerosis (MS), the most common immune-mediated and demyelinating disease of the central nervous system. However, the contribution of adipose tissue to the etiology and progression of MS is still obscure. This study aimed at deciphering the responses of AT in experimental autoimmune encephalomyelitis (EAE), the best characterized animal model of MS.
View Article and Find Full Text PDFCancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability.
View Article and Find Full Text PDFA balanced diet is critical for human health, and edible plants play an important role in providing essential micronutrients as well as specific microRNAs (miRNAs) that can regulate human gene expression. Here we present the effects of (MO) miRNAs (-miRs) on lipid metabolism. Through studies we identified the potential genes involved in lipid metabolism targeted by -miRs.
View Article and Find Full Text PDFBrown adipose tissue (BAT) controls mammalian core body temperature by non-shivering thermogenesis. BAT is extraordinarily rich in mitochondria, which have the peculiarity of generating heat by uncoupled respiration. Since the mitochondrial activity of BAT is subject to cycles of activation and deactivation in response to environmental temperature changes, an integrated mitochondrial quality control (MQC) system is of fundamental importance to ensure BAT physiology.
View Article and Find Full Text PDFCell senescence is critical in diverse aspects of organism life. It is involved in tissue development and homeostasis, as well as in tumor suppression. Consequently, it is tightly integrated with basic physiological processes during life.
View Article and Find Full Text PDFRecent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program.
View Article and Find Full Text PDFPsoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated scaly plaques. Oxidative stress plays a crucial role in the psoriasis pathogenesis and is associated with the disease severity. Dimethyl fumarate modulates the activity of the pro-inflammatory transcription factors.
View Article and Find Full Text PDFRecent studies demonstrated reduced blood lysosomal acid lipase (LAL) activity in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to verify hepatic LAL protein content and activity in in vitro and in vivo models of fat overload and in NAFLD patients. LAL protein content and activity were firstly evaluated in Huh7 cells exposed to high-glucose/high-lipid (HGHL) medium and in the liver of C57BL/6 mice fed with high-fat diet (HFD) for 4 and 8 months.
View Article and Find Full Text PDFFerroptosis is an iron-dependent cell death caused by impaired glutathione metabolism, lipid peroxidation and mitochondrial failure. Emerging evidences report a role for ferroptosis in Friedreich's Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of the mitochondrial protein frataxin. Nrf2 signalling is implicated in many molecular aspects of ferroptosis, by upstream regulating glutathione homeostasis, mitochondrial function and lipid metabolism.
View Article and Find Full Text PDFBackground: Friedreich's ataxia (FRDA) is a neurodegenerative disease characterized by early mortality due to hypertrophic cardiomyopathy. FRDA is caused by reduced levels of frataxin (FXN), a mitochondrial protein involved in the synthesis of iron-sulphur clusters, leading to iron accumulation at the mitochondrial level, uncontrolled production of reactive oxygen species and lipid peroxidation. These features are also common to ferroptosis, an iron-mediated type of cell death triggered by accumulation of lipoperoxides with distinct morphological and molecular characteristics with respect to other known cell deaths.
View Article and Find Full Text PDFA common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles. Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress. Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle.
View Article and Find Full Text PDFLow-protein/high-carbohydrate (LPHC) diet has been suggested to promote metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT).
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
October 2020
Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD.
View Article and Find Full Text PDFBrown and subcutaneous adipose tissues play a key role in non-shivering thermogenesis both in mice and human, and their activation by adrenergic stimuli promotes energy expenditure, reduces adiposity, and protects against age-related metabolic diseases such as type 2 diabetes (T2D). Low-grade inflammation and insulin resistance characterize T2D. Even though the decline of thermogenic adipose tissues is well-established during ageing, the mechanisms by which this event affects immune system and contributes to the development of T2D is still poorly defined.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is associated with aging and features of metabolic syndrome. Lipotoxicity and oxidative stress are consequent to dysregulation of lipid metabolism and lipid accumulation, leading to hepatocyte injury and inflammation. Lipophagy consists in selective degradation of intracellular lipid droplets by lysosome and mounting evidence suggests that lipophagy is dysregulated in NAFLD.
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