beige fat

Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form...

In the cold, the absence of the mitochondrial uncoupling protein-1 (UCP1) results in hyper-recruitment of beige fat, but classical brown fat becomes atrophied. Here we examine possible mechanisms underlying this phenomenon. We confirm that in brown fat from UCP1-KO mice acclimated to the cold, the levels of mitochondrial respiratory chain proteins were diminished; however, in beige fat the mitochondria seemed to be unaffected. The macrophages that accumulated massively not only in brown fat but also in beige fat of the UCP1-KO mice acclimated to cold did not express tyrosine hydroxylase, the norepinephrine transporter (NET) and monoamine oxidase-A (MAO-A)...

Connexin43 (Cx43) is the most abundant gap junction protein present in the mesenchymal lineage. In mature adipocytes, Cx43 mediates white adipose tissue (WAT) "beiging" in response to cold exposure and maintains the mitochondrial integrity of brown adipose tissue (BAT). We found that genetic deletion of Gja1 (Cx43 gene) in cells that give rise to chondro-osteogenic and adipogenic precursors driven by the Dermo1/Twist2 promoter led to lower body adiposity and partial protection against the weight gain and metabolic syndrome induced by a high fat diet (HFD) in both sexes...

The appropriate transcriptional activity of PPARγ is indispensable for controlling inflammation, tumor and obesity. Therefore, the identification of key switch that couples PPARγ activation with degradation to sustain its activity homeostasis is extremely important. Unexpectedly, we here show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) critically controls PPARγ activity homeostasis via SIRT1 to enhance adipose plasticity via promoting white adipose tissues beiging and brown adipose tissues thermogenesis...

Global health concerns about micro- and nanoplastics are increasing. The newly discovered beige adipocytes play a vital role in energy homeostasis through their high thermogenic capacity upon activation. However, the effects of micro- and nanoplastics on beige adipocytes have not yet been studied. We investigated whether the effects of oral exposure to polystyrene nanoparticles (PS-NPs) on systemic metabolic performance can be induced by disrupting beige adipocyte function, and the potential mechanism. In the present study, C57BL/6 J male mice were fed a high-fat diet (HFD) with or without PS-NPs exposure for 12 weeks to investigate the differences in metabolic performance...

The antiobesity effect of conjugated linoleic acid (CLA) has been reported. However, the underlying mechanisms have not been fully clarified. Thus, this study aimed to investigate the effects of CLA on thermogenesis of interscapular brown adipose tissue (iBAT) and browning of inguinal subcutaneous white adipose tissue (iWAT) and explore the possible signaling pathway. The in vivo results showed that CLA enhanced the O2 consumption and heat production in HFD (high-fat diet)-fed female mice by roughly 38%. Meanwhile, CLA increased the average iBAT temperature by 2°C at the room temperature and cold exposure, respectively...

Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NO·) in AT (dys)function in relation to developing T2D...

In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates...

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremities fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines and inflammatory markers were assessed in 46 MMA subjects and 99 matched controls...

Connexin43 (Cx43) is the most abundant gap junction protein present in the mesenchymal lineage. In mature adipocytes, Cx43 mediates white adipose tissue (WAT) "beiging" in response to cold exposure and maintains the mitochondrial integrity of brown adipose tissue (BAT). We found that genetic deletion of Gja1 (Cx43 gene) in cells that give rise to chondro-osteogenic and adipogenic precursors driven by the Dermo1/Twist2 promoter leads to lower body adiposity and partial protection against the weight gain and metabolic syndrome induced by a high fat diet (HFD) in both sexes...

Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD mouse model...

Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light-crosslinking. We used human white adipose tissue-derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel...

Intermittent cold exposure (ICE) has garnered increased attention in popular culture, largely for its proposed effects on mood and immune function, but there are also suggestions that the energy-wasting mechanisms associated with thermogenesis may decrease body weight and fat mass. Considering the continued and worsening prevalence of obesity and type II diabetes, any protocol that can reduce body weight and/or improve metabolic health would be a substantial boon. Here, we present a narrative review exploring the research related to ICE and adipose tissue...

Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show that the cAMP-binding protein EPAC1 is a central regulator of adaptive BAT growth. In vivo, selective pharmacological activation of EPAC1 increases BAT mass and browning of white fat, leading to higher energy expenditure and reduced diet-induced obesity. Mechanistically, EPAC1 coordinates a network of regulators for proliferation specifically in thermogenic adipocytes, but not in white adipocytes...

BACKGROUND: The fat retention rate is associated with postoperative inflammation. However, fat survival is still unpredictable even when supplemented with adipose-derived stem cells (ADSCs). Beige adipocytes play a role in regulating pathological inflammation. Thus, we assumed that exosomes may promote macrophage polarization to regulate inflammation when we simulated postgrafted inflammation by lipopolysaccharide (LPS) induction. METHODS: 3T3-L1 preadipocytes were used to differentiate into beige adipocytes, which were stimulated by special culture media, and then, exosomes were isolated from the supernatant...

Fat browning, which converts white adipose tissue to brown, has attracted attention as a promising strategy for the treatment of obesity. Betanin (BT) has been reported to have potential anti-obesity activity. 3T3-L1 cells were differentiated for 7 days during BT treatment. The BT concentration range for the study was determined using an MTT assay, and lipid accumulation was evaluated by Oil-Red-O staining. The expression of protein level was analyzed by Western blot. Immunofluorescence images were performed with confocal microscopy to visually show the amount and location of thermogenesis factor uncoupling protein1 (UCP1) and mitochondria...

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3 ) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs...

OBJECTIVE: Fibroblast activation protein α (FAP) is expressed in normal adipose tissue and related to some pleiotropic metabolic regulators. However, the exact role and mechanism of FAP in obesity and related metabolic disorders are not well understood. METHODS: FAP knockout mice were fed a normal diet or a high-fat diet (HFD) for 12 weeks. FAP knockout mice or wild-type mice treated with an FAP inhibitor were subjected to cold stress for 5 days...

PURPOSE OF REVIEW: Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment...

With age, people tend to accumulate body fat and reduce energy expenditure 1 . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles 2,3 . The activity of brown and beige depots inversely correlates with BMI and age 4-11 , suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease 12-15 . Heme is an enzyme cofactor and signaling molecule that we recently showed to regulate BAT function 16 ...