Hyaluronan Mediates Cold-Induced Adipose Tissue Beiging.

Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different.

Mammalian IRE1α dynamically and functionally coalesces with stress granules.

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs).

Depletion of JunB increases adipocyte thermogenic capacity and ameliorates diet-induced insulin resistance.

The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. Here we show that in male mice, a population of transcription factor jun-B (JunB)-enriched (JunB) adipocytes within the brown adipose tissue exhibits lower thermogenic capacity compared to high-thermogenic adipocytes.

FASN deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress.

Fatty acid synthase (FASN) maintains de novo lipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-coenzyme A (CoA) is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation. Here, we show that reductive carboxylation also occurs in the absence of DNL.

Becoming less beige with age.

The production of beige adipocytes following cold exposure is blocked as mice get older and leads to changes in the expression of metabolic genes.

FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress.

Fatty acid synthase (FASN) maintains lipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-CoA is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation under hypoxia. Here we show that reductive carboxylation also occurs in the absence of DNL in cells with defective FASN.

Adipose Tissue Plasticity in Aging.

As a dynamic endocrine organ, white adipose tissue (WAT) stores lipids and plays a critical role in maintaining whole-body energy homeostasis and insulin sensitivity. A large group of the population over 65 years old suffer from increased WAT mass, especially in the visceral location. Visceral adiposity accelerates aging through promoting age-associated chronic conditions, significantly shortening life expectancy.

Adipocyte IRE1α promotes PGC1α mRNA decay and restrains adaptive thermogenesis.

Adipose tissue undergoes thermogenic remodeling in response to thermal stress and metabolic cues, playing a crucial role in regulating energy expenditure and metabolic homeostasis. Endoplasmic reticulum (ER) stress is associated with adipose dysfunction in obesity and metabolic disease. It remains unclear, however, if ER stress-signaling in adipocytes mechanistically mediates dysregulation of thermogenic fat.

Metabolic reprogramming in the OPA1-deficient cells.

OPA1, a dynamin-related GTPase mutated in autosomal dominant optic atrophy, is essential for the fusion of the inner mitochondrial membrane. Although OPA1 deficiency leads to impaired mitochondrial morphology, the role of OPA1 in central carbon metabolism remains unclear. Here, we aim to explore the functional role and metabolic mechanism of OPA1 in cell fitness beyond the control of mitochondrial fusion.

Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels and Neonate Growth in Mice.

Breastfeeding offers a broad spectrum of health benefits for infants. However, overnutrition and a steady increase in maternal obesity in the U.S.

The B56α subunit of PP2A is necessary for mesenchymal stem cell commitment to adipocyte.

Adipose tissue plays a major role in maintaining organismal metabolic equilibrium. Control over the fate decision from mesenchymal stem cells (MSCs) to adipocyte differentiation involves coordinated command of phosphorylation. Protein phosphatase 2A plays an important role in Wnt pathway and adipocyte development, yet how PP2A complexes actively respond to adipocyte differentiation signals and acquire specificity in the face of the promiscuous activity of its catalytic subunit remains unknown.

Energy metabolism in brown adipose tissue.

Brown adipose tissue (BAT) is well known to burn calories through uncoupled respiration, producing heat to maintain body temperature. This 'calorie wasting' feature makes BAT a special tissue, which can function as an 'energy sink' in mammals. While a combination of high energy intake and low energy expenditure is the leading cause of overweight and obesity in modern society, activating a safe 'energy sink' has been proposed as a promising obesity treatment strategy.

Brown Adipose Tissue Heterogeneity, Energy Metabolism, and Beyond.

Brown adipocyte in brown adipose tissue (BAT) specializes in expending energy through non-shivering thermogenesis, a process that produces heat either by uncoupling protein 1 (UCP1) dependent uncoupling of mitochondrial respiration or by UCP1 independent mechanisms. Apart from this, there is ample evidence suggesting that BAT has an endocrine function. Studies in rodents point toward its vital roles in glucose and lipid homeostasis, making it an important therapeutic target for treating metabolic disorders related to morbidities such as obesity and type 2 diabetes.

Chronic cold exposure enhances glucose oxidation in brown adipose tissue.

The cultured brown adipocytes can oxidize glucose in vitro, but it is still not fully clear whether brown adipose tissue (BAT) could completely oxidize glucose in vivo. Although positron emission tomography (PET) with F-fluorodeoxyglucose ( F-FDG) showed a high level of glucose uptake in the activated BAT, the non-metabolizable F-FDG cannot fully demonstrate intracellular glucose metabolism. Through in vivo [U- C]glucose tracing, here we show that chronic cold exposure dramatically activates glucose oxidation in BAT and the browning/beiging subcutaneous white adipose tissue (sWAT).

Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer.

Background: Previous studies suggested that mdivi-1 (mitochondrial division inhibitor), a putative inhibitor of dynamin-related protein (DRP1), decreased cancer cell proliferation through inducing mitochondrial fusion and altering oxygen consumption. However, the metabolic reprogramming underlying the DRP1 inhibition is still unclear in cancer cells.

Methods: To better understand the metabolic effect of DRP1 inhibition, [U-C]glucose isotope tracing was employed to assess mdivi-1 effects in several cancer cell lines, DRP1-WT (wild-type) and DRP1-KO (knockout) H460 lung cancer cells and mouse embryonic fibroblasts (MEFs).

Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue.

Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT.

Cellular Origins of Beige Fat Cells Revisited.

Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precursors or through reprogramming of mature white adipocytes has been a topic of intense discussion.

Remodeling of Murine Mammary Adipose Tissue during Pregnancy, Lactation, and Involution.

White adipocytes in the mammary gland stroma comprise the majority of the mammary gland mass. White adipocytes regulate numerous hormonal and metabolic processes and exhibit compositional and phenotypic plasticity. This plasticity is exemplified by the ability of mammary adipocytes to regress during lactation, when mammary epithelial cells expand to establish sufficient milk-producing alveoli.

Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice.

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear.

Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation.

Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation and the developmental origin of the re-appearing adipocyte post involution are unclear.

Peroxisome Proliferator-Activated Receptor γ and Its Role in Adipocyte Homeostasis and Thiazolidinedione-Mediated Insulin Sensitization.

Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both and However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death.

Short-Term Versus Long-Term Effects of Adipocyte Toll-Like Receptor 4 Activation on Insulin Resistance in Male Mice.

Chronic exposure to high-saturated fat diets (HFDs) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance. A possible mediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocyte-specific deletion of TLR4 in a mouse model that is referred to as the "Tadipo" mouse.

Autonomous interconversion between adult pancreatic α-cells and β-cells after differential metabolic challenges.

Background: Evidence hints at the ability of β-cells to emerge from non-β-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous β-cell regeneration without genetic or pharmacological manipulations remain to be determined.

Methods & Results: Using PANIC-ATTAC mice, a model of titratable, acute β-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of residual tamoxifen activity is crucial for β-cell lineage tracing studies using the tamoxifen-inducible Cre/loxP systems.