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The epidemic of fat-related metabolic disorders necessitates innovative therapies. Here, the authors show adipose-resident c-kit⁺ cells are crucial brown adipocyte progenitors and provide a promising way to manipulate adult brown adipose tissue for combating obesity and metabolic disorders.

Inhibition of haem synthesis is shown to lead to the accumulation of branched-chain amino acids in the brown adipose tissue of mice, which reduces UCP1 levels and impairs thermogenesis.

Adipose tissue accommodates large volume changes upon expansion, but the molecular mechanisms involved are not fully understood. Here, Aboy et al. describe CAV1 Y14 phosphorylation as required for appropriate adipocyte caveolae flattening and homeostasis.

Obesity is a risk factor for diseases. Here, authors found that inhibition of cyclin-dependent kinase 6 increased de novo lipogenesis in the adipose tissues but not in the liver, which may provide a strategy to concur obesity-induced maladies.

Zhang et al. show that in mice, an adipocyte population with high expression of the transcription factor JunB in the brown adipose tissue shows reduced thermogenic capacity. Depletion of JunB increases the fraction of adipocytes with high thermogenic capacity and ameliorates diet-induced insulin resistance.

Adipose tissue harbors functionally distinct progenitor cell subsets. Using scRNAseq and functional assays, we disclose a pathogenic adipose progenitor subset, which impairs glycose homeostasis through the construction of a detrimental niche.

Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.

Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, the authors show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response as a protective mechanism.

Obesity impairs regulation of adipocyte lipolysis, which contributes towards development of insulin resistance. Here the authors report that adipocyte Gq signaling functions as a regulator of lipolysis and systemic glucose and lipid homeostasis in mice, suggesting that agents able to stimulate this pathway may prove useful as antidiabetic drugs.

Brown adipose tissue (BAT) in infants has been studied for more than a century, however, the knowledge about its physiological features is limited. Here, the authors investigate the link between BAT thermogenesis and the regulation of temperature in human new-borns with non-invasive infrared thermography.

Lipolysis in adipose tissue releases fatty acids during fasting. Here, authors show that ApoL6, a lipid droplet-associated protein, is specifically expressed in adipocytes upon feeding to inhibit lipolysis by directly interacting with Perilipin 1 to competitively inhibit Perilipin 1-HSL interaction.

The origin of the heterogeneity of metabolic and inflammatory profiles exhibited by white adipocytes is little understood. Here, using scRNA-seq and computational methods, the authors show that differentiating preadipocytes exhibit gene expression differences and suggest underlying regulators.

Myf5 lineage precursor cells give rise to brown adipocytes. Here, the authors show that the Myf5 lineage, as well as the Pax3 lineage, contribute to white and brite mature adipocytes and describe the effects of Myf5 lineage-specific deletion of the insulin receptor on adipose tissue formation in mice.

Insulin resistance in adipose tissue is a hallmark of obesity. Here, the authors generate inducible adipocyte-specific PTEN knockout mice to demonstrate that enhanced insulin sensitivity in adipose tissue is directly linked to improved systemic metabolic homeostasis, despite an increase in fat mass.

Mutations in the FTO gene have been linked to obesity. Here, Merkestein et al. provide in vitro and in vivo evidence that FTOdirectly regulates adipogenesis in mice at the stage of mitotic clonal expansion, likely by modulating the expression of the transcription factor RUNX1T1.

Current methods to image brown adipose tissue rely on radioactive tracers and specialized imaging equipment. Here Azhdarinia et al.report a peptide-based probe that selectively binds to the vascular endothelium of brown adipose tissue and allows the near-infrared imaging of brown fat in mice.

Unlike rodents, humans produce the protein Cidea in white adipose tissue, where it associates with lipid droplets. Here the authors generate mice that express human Cidea in fat tissues to show Cidea exerts beneficial metabolic effects by regulating the expansion of visceral fat in response to a high-fat diet.

Central to the lineage commitment of multipotent mesenchymal stem cells is the nuclear receptor PPARγ, the master regulator of adipogenesis. Here the authors use a variety of structural approaches to rationally design PPARγ inverse agonist SR2595, and demonstrate its ability to promote osteogenesis.

The enzyme soluble guanylyl cyclase (sGC) regulates differentiation of brown fat. Here, Hoffman et al.show that a small molecule sGC stimulator increases brown fat activity and browning of white fat, thereby inducing energy expenditure, weight loss and partial protection from diet-induced obesity in mice.

Although thyroid hormone (TH) has anti-obesity potential, systemic administration of TH causes severe adverse effects without obvious weight loss. Here, the authors show that adipose tissue-targeted delivery of TH with liposomes is a safe and efficient strategy to treat obesity and its related complications in mice.

Disruption of CREB/CRTC2, a key gluconeogenic transcriptional complex, has been shown to ameliorate insulin resistance in mice. Here, the authors show that the inhibitor artipllin C and the synthetic compound A57, which presents with higher inhibitory activity, improve insulin sensitivity in obese mice by inhibiting CREB-CRTC2 interaction.

Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

Adipose tissue varies depending on localization. Vijay et al. perform single-cell RNA sequencing in multiple adipose tissue depots from obese individuals and identify distinct subpopulations of endothelial cells, immune cells and pre-adipocytes.

The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.

Brown adipocytes are rich in mitochondria and influence whole-body energy balance. Here, Duteil et al. show that the lysine-specific demethylase 1 (LSD1) controls mitochondrial biogenesis and the formation of brown-like adipocytes, and that LSD1 overexpression in white fat reduces weight gain of mice on a high-fat diet.

Pro-inflammatory NF-κB signalling is regulated by protein sumoylation. Here the authors show that lack of the desumoylating protease SENP1 in fat tissue induces NF-κB activity and inflammation in peri-pancreatic adipocytes, leading to symptoms of type 1 diabetes in mice.

Bone marrow contains adipocytes, which have been thought to form one type of marrow adipose tissue (MAT). Here, the authors identify two MAT subpopulations in mice and humans—‘regulated’ and ‘constitute’ MAT—which show distinct phenotypic and cellular traits, and respond differently to cold exposure.

Bmp signalling is required for adult muscle maintenance and growth. Here, the authors show that ablating the expression of Bmp receptor 1a in mouse myo-endothelial cells increases intramuscular adipogenesis.

The kinase Lkb1 is expressed in various metabolic tissues and is known to regulate cellular and systemic energy homeostasis. Here, the authors delete Lkb1 specifically in mature adipocytes of mice to show that Lkb1 regulates brown adipose tissue expansion and expression of UCP1.

Demethylase JMJD1A activates thermogenesis-related target genes in response to β-adrenergic hormones. Here, the authors show that phosphorylation of JMJD1A at S265 increases its interaction with the SWI/SNF chromatin remodeler, leading to long-range chromatin interactions and target gene activation.

Adipocyte differentiation is accompanied by large scale changes in the actin cytoskeleton. Here, Nobusue et al.show that binding to G-actin sequesters the transcriptional coactivator MKL1 in the cytoplasm, and triggers differentiation by inducing the expression of pro-adipogenic transcription factor PPARγ.

Berberine is contained in some plant-derived medicines and is known to have anti-diabetic effects. Here the authors show that berberine activates thermogenesis in white and brown adipose tissues, thereby increasing organismal energy expenditure and limiting weight gain in genetically obese mice.

Tip60 is a transcriptional coregulator that has an important role in differentiation. Here, Gao et al. demonstrate that the deubiquitination of Tip60 by USP7, a dominant deubiquitinating enzyme, is a key mechanism in early adipogenesis regulation.

This Review outlines changes in endocrine and metabolic function that occur in various adipose tissue depots during ageing and explains how these alterations contribute to age-related decline in metabolic health. The Review also discusses how various treatments might slow this decline by improving adipose tissue function.

Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.

Adipose tissue progenitor cells regulate adipose remodelling and local and systemic metabolism in response to factors such as calorie intake and hormone signalling. Here, the authors discuss the current understanding of adipose progenitor subtypes, the plasticity of these cell types and their roles in metabolic health and disease.

Circulating microRNAs act as a new class of endocrine factor that can facilitate crosstalk between metabolic organs. This Review highlights obesity-associated and/or adipose tissue-enriched microRNAs and discusses their potential as biomarkers or therapeutics for obesity and related disorders.

This Review provides an up-to-date overview of the lipolytic effects of growth hormone (GH), setting current knowledge into the context of historical data. In addition, the molecular mechanisms of GH-induced lipolysis and insulin resistance as well as the actions of GH on different adipose tissue depots and adipocyte subsets are discussed.

This Review provides an overview of the extensive crosstalk between adipocytes, resident innate immune cells and the sympathetic nerves that innervate adipose tissue, as well as the changes that occur in these secretory and signalling pathways in obesity.

This Review examines the origins of marrow adipocytes and their function under normal or pathological conditions. Regulation of bone marrow adipose tissue by nutrient status is considered, as well as the interactions between bone marrow adipose tissue, haematopoietic cells of the bone marrow and the bone.

The brain regulates adipose tissue metabolism through sympathetic efferent pathways; in turn, adipose tissues relay energy-status information to the brain. This Review gives an overview of interactions between the brain and adipose tissues, with a particular focus on leptin as a regulator of these communications.

This Review summarizes the current knowledge on the biology and regional variability of the adipose tissue, highlighting the molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system. Current state-of-the-art techniques in adipose tissue imaging for cardiovascular risk stratification and the potential of the adipose tissue as a target for the treatment of cardiovascular disease are also described.

Cellular metabolic demand skyrockets during intense exercise, thus rendering the communication of metabolic state essential for organismal homeostasis. Murphy, Watt and Febbraio discuss the physiological processes governing intertissue communication during exercise and the molecules mediating such cross-talk.

This Review examines the signalling between cells resident in adipose tissue and local sensory and sympathetic nerve fibres. The potential of targeting these processes in new therapeutics for metabolic diseases is also discussed.

Targeting thermogenesis in brown fat and skeletal muscle to expend energy and reduce fat mass is a promising therapeutic strategy for treating obesity and related metabolic diseases. Here, Betz and Enerbäck discuss the different molecular pathways regulating thermogenesis in these organs and discuss how they can be therapeutically exploited.