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Nutrients Mar 2023Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has... (Review)
Review
Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.
Topics: Humans; Gastrointestinal Microbiome; Obesity; Adipose Tissue, White; Adipose Tissue, Brown; Mitochondria; Thermogenesis; Energy Metabolism
PubMed: 37049562
DOI: 10.3390/nu15071723 -
International Journal of Biological... 2022Mammals maintain a constant core body temperature through adaptive thermogenesis which includes shivering and non-shivering thermogenesis. Non-shivering thermogenesis... (Review)
Review
Mammals maintain a constant core body temperature through adaptive thermogenesis which includes shivering and non-shivering thermogenesis. Non-shivering thermogenesis relies primarily on mitochondrial uncoupling protein 1 (UCP1) in thermogenic fat (including brown and beige adipose tissue) to burn substrates, such as fatty acids (FAs), and convert chemical energy into heat. Lipid droplets (LDs), which are organelles that store lipids, are present in large numbers in thermogenic fat and are essential for adipose thermogenesis. Upon cold stimulation, LDs rapidly release FAs through autophagy or lipase-mediated lipolysis and rapidly translocate FAs into the mitochondria by interacting with mitochondria to burn and so promote thermogenesis. In addition, LD proteins promote the expression of UCP1 by activating the transcriptional activity of thermogenesis-related proteins. Here, the progress of research on the important role of LDs in thermogenesis is reviewed, mainly in terms of LD proteins, LD-organelle interactions, and LD autophagy (lipophagy). The emerging rationale for the involvement of LDs in each thermogenic pathway is described and the remaining unanswered questions in this field are highlighted.
Topics: Animals; Lipid Droplets; Thermogenesis; Uncoupling Protein 1; Adipose Tissue; Mitochondria; Mammals
PubMed: 36439883
DOI: 10.7150/ijbs.77051 -
Hormone Research in Paediatrics 2022To regulate body temperature, mammals possess brown adipose tissue (BAT), which converts significant amounts of chemical energy into heat. Due to its remarkable energy... (Review)
Review
BACKGROUND
To regulate body temperature, mammals possess brown adipose tissue (BAT), which converts significant amounts of chemical energy into heat. Due to its remarkable energy demand, BAT is currently discussed as a target organ to treat obesity and obesity-related disorders.
SUMMARY
Although BAT is predominantly present in infants and its relative mass declines with age, new findings suggest that BAT has a relevant role in the regulation of energy homeostasis as well as in the regulation of the energy substrates glucose and lipids in older children, adolescents, and adults. In this overview, we will outline basic mechanisms of BAT thermogenesis and the recently described physiological relevance of BAT in metabolism in children and adolescents.
KEY MESSAGE
The connection of BAT activity with glucose metabolism and insulin sensitivity seems to be evident from recent studies, implicating BAT as an important influencing factor in the context of metabolic syndrome.
Topics: Adipose Tissue, Brown; Adolescent; Adult; Animals; Child; Energy Metabolism; Humans; Mammals; Metabolic Syndrome; Obesity; Thermogenesis
PubMed: 34348306
DOI: 10.1159/000518353 -
Frontiers in Endocrinology 2021Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the... (Review)
Review
Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the epidemic of metabolic syndromes such as obesity and type 2 diabetes. These thermogenic fats implement mitochondrial oxidative phosphorylation and uncouple respiration to catabolize fatty acids and glucose, which leads to an increase in energy expenditure. In particular, beige adipocytes that arise in white adipose tissue display their thermogenic capacity through various noncanonical mechanisms. This review aims to summarize the general overview of thermogenic fat, especially including the UCP1-independent adaptive thermogenesis and the emerging mechanisms of "beiging", which may provide more evidence of targeting thermogenic fat to counteract obesity and other metabolic disorders in humans.
Topics: Adipocytes, Beige; Adipose Tissue; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Energy Metabolism; Humans; Lipid Metabolism; Lipolysis; Thermogenesis
PubMed: 34367068
DOI: 10.3389/fendo.2021.696505 -
Advanced Science (Weinheim,... Oct 2023Mitochondria are the pivot organelles to control metabolism and energy homeostasis. The capacity of mitochondrial metabolic adaptions to cold stress is essential for...
Mitochondria are the pivot organelles to control metabolism and energy homeostasis. The capacity of mitochondrial metabolic adaptions to cold stress is essential for adipocyte thermogenesis. How brown adipocytes keep mitochondrial fitness upon a challenge of cold-induced oxidative stress has not been well characterized. This manuscript shows that IFI27 plays an important role in cristae morphogenesis, keeping intact succinate dehydrogenase (SDH) function and active fatty acid oxidation to sustain thermogenesis in brown adipocytes. IFI27 protein interaction map identifies SDHB and HADHA as its binding partners. IFI27 physically links SDHB to chaperone TNF receptor associated protein 1 (TRAP1), which shields SDHB from oxidative damage-triggered degradation. Moreover, IFI27 increases hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) catalytic activity in β-oxidation pathway. The reduced SDH level and fatty acid oxidation in Ifi27-knockout brown fat results in impaired oxygen consumption and defective thermogenesis. Thus, IFI27 is a novel regulator of mitochondrial metabolism and thermogenesis.
Topics: Succinic Acid; Adipocytes, Brown; Adipose Tissue, Brown; Fatty Acids; Thermogenesis
PubMed: 37544897
DOI: 10.1002/advs.202301855 -
Cellular and Molecular Life Sciences :... Nov 2023Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been...
Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.
Topics: Mice; Humans; Animals; Obesity; Adipose Tissue, Brown; Adipocytes, Brown; Adipose Tissue, White; Peptides; Thermogenesis; Mice, Inbred C57BL
PubMed: 38010450
DOI: 10.1007/s00018-023-05027-9 -
Current Obesity Reports Mar 2022This review highlights aspects of brown adipose tissue (BAT) communication with other organ systems and how BAT-to-tissue cross-talk could help elucidate future obesity... (Review)
Review
PURPOSE OF REVIEW
This review highlights aspects of brown adipose tissue (BAT) communication with other organ systems and how BAT-to-tissue cross-talk could help elucidate future obesity treatments.
RECENT FINDINGS
Until recently, research on BAT has focused mainly on its thermogenic activity. New research has identified an endocrine/paracrine function of BAT and determined that many BAT-derived molecules, termed "batokines," affect the physiology of a variety of organ systems and cell types. Batokines encompass a variety of signaling molecules including peptides, metabolites, lipids, or microRNAs. Recent studies have noted significant effects of batokines on physiology as it relates whole-body metabolism and cardiac function. This review will discuss batokines and other BAT processes that affect the liver, cardiovascular system, skeletal muscle, immune cells, and brown and white adipose tissue. Brown adipose tissue has a crucial secretory function that plays a key role in systemic physiology.
Topics: Adipose Tissue, Brown; Energy Metabolism; Humans; Muscle, Skeletal; Thermogenesis
PubMed: 34997461
DOI: 10.1007/s13679-021-00465-7 -
Autophagy Mar 2023Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a...
Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. specific- ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications.
Topics: Mice; Humans; Animals; Adipose Tissue, Brown; PPAR gamma; Autophagy; Obesity; Thermogenesis; Nuclear Proteins; Nuclear Receptor Co-Repressor 1
PubMed: 35947488
DOI: 10.1080/15548627.2022.2111081 -
Journal of Visualized Experiments : JoVE Jul 2022Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. Surprisingly...
Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. Surprisingly little evidence is available to link the neural, myocellular, and molecular mechanisms of thermogenesis directly to measurable changes in muscle temperature. This paper describes a method in which temperature transponders are utilized to retrieve direct measurements of mouse and rat skeletal muscle temperature. Remote transponders are surgically implanted within the muscle of mice and rats, and the animals are given time to recover. Mice and rats must then be repeatedly habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage. Muscle temperature can also be measured during prescribed physical activity (i.e., treadmill walking at a constant speed) to factor out changes in activity as contributors to the changes in muscle temperature induced by these stimuli. This method has been successfully used to elucidate mechanisms underlying muscle thermogenic control at the level of the brain, sympathetic nervous system, and skeletal muscle. Provided are demonstrations of this success using predator odor (PO; ferret odor) as a contextual stimulus and injections of oxytocin (Oxt) as a pharmacological stimulus, where predator odor induces muscle thermogenesis, and Oxt suppresses muscle temperature. Thus, these datasets display the efficacy of this method in detecting rapid changes in muscle temperature.
Topics: Adipose Tissue, Brown; Animals; Energy Metabolism; Ferrets; Muscle, Skeletal; Rats; Sympathetic Nervous System; Thermogenesis
PubMed: 35969093
DOI: 10.3791/64264 -
Frontiers in Endocrinology 2023Obesity occurs when overall energy intake surpasses energy expenditure. White adipose tissue is an energy storage site, whereas brown and beige adipose tissues... (Review)
Review
Obesity occurs when overall energy intake surpasses energy expenditure. White adipose tissue is an energy storage site, whereas brown and beige adipose tissues catabolize stored energy to generate heat, which protects against obesity and obesity-associated metabolic disorders. Metabolites are substrates in metabolic reactions that act as signaling molecules, mediating communication between metabolic sites (i.e., adipose tissue, skeletal muscle, and gut microbiota). Although the effects of metabolites from peripheral organs on adipose tissue have been extensively studied, their role in regulating adipocyte thermogenesis requires further investigation. Skeletal muscles and intestinal microorganisms are important metabolic sites in the body, and their metabolites play an important role in obesity. In this review, we consolidated the latest research on skeletal muscles and gut microbiota-derived metabolites that potentially promote adipocyte thermogenesis. Skeletal muscles can release lactate, kynurenic acid, inosine, and β-aminoisobutyric acid, whereas the gut secretes bile acids, butyrate, succinate, cinnabarinic acid, urolithin A, and asparagine. These metabolites function as signaling molecules by interacting with membrane receptors or controlling intracellular enzyme activity. The mechanisms underlying the reciprocal exchange of metabolites between the adipose tissue and other metabolic organs will be a focal point in future studies on obesity. Furthermore, understanding how metabolites regulate adipocyte thermogenesis will provide a basis for establishing new therapeutic targets for obesity.
Topics: Humans; Adipose Tissue, Brown; Gastrointestinal Microbiome; Adipocytes; Obesity; Thermogenesis; Muscle, Skeletal
PubMed: 37867516
DOI: 10.3389/fendo.2023.1265175