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Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Neri et al. develop elegant tools to understand how the sympathetic nervous system regulates intrascapular brown adipose tissue (iBAT) function. Using these tools, they find that sympathetic nerves targeting the iBAT parenchyma control local blood flow and heat production, while those innervating the iBAT vasculature regulate systemic glucose metabolism.

Elevated triglyceride levels often occur in obesity and can contribute to cardiovascular disease. Brown adipose tissue (BAT) is known to burn fat, and now Joerg Heeren and his colleagues show that BAT actively takes up triglycerides in cold conditions, suggesting a possible therapy to lower triglyceride levels in states of obesity.

Untargeted metabolomics demonstrate that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched, and inosine is identified as a metabolite released during apoptosis regulating thermogenic fat and counteracting obesity.

The development of beige adipocytes in white adipose tissue, so called browning, could help to improve metabolic health. This Review discusses the development and regulatory control of beige adipocytes as well as their role in metabolism.

Brown adipose tissue (BAT) produces heat by burning lipid triglycerides. Here, Berbée et al. show that pharmacological BAT activation protects hyperlipidemic mice from atherosclerosis, provided mice retain the metabolic capacity to clear cholesterol-enriched lipoprotein remnants by the liver.

Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.

In mouse and nonhuman primate models, treatment with selective, long-acting neurokinin 2 receptor agonists aids weight loss by suppressing appetite and increasing energy expenditure, as well as by increasing insulin sensitivity.

Reverte-Salisa et al. show that, in preadipocytes, EPAC1 enhances brown adipose tissue growth and increases the function of thermogenic fat in obesogenic conditions. Activation of EPAC1 induces human brown adipocyte proliferation and differentiation.

The livers of obese mice and humans show increased levels of miR-802 resulting in impaired glucose tolerance and decreased insulin sensitivity through silencing of Hnf1b, revealing a novel pathway with potential relevance for type 2 diabetes.

Exosomes are RNA-containing lipid vesicles with roles in inter-tissue crosstalk. Here the authors show that exosome release from brown adipocytes is increased upon thermogenic activation, both in vitro and in vivo, and demonstrate that serum levels of exosomal miR-92 reflect brown fat activity in humans.

Mitochondria have a pivotal role in the transport of dietary lipids in enterocytes, a finding that might have relevance to understanding the aberrant gastrointestinal function in patients with mitochondrial disorders.

Polyunsaturated Fatty Acids (PUFA), such as omega-3 fatty acids, are recognized for their lipid lowering and anti-inflammatory properties. Here, the authors show that endogenous lipid synthesis controls the use of PUFA and thus determine the therapeutic benefit of omega-3 fatty acid supplementation.

Cholesterol transport is tightly regulated in the cell and in lysosomes is regulated by NPC1/2. Here, Heybrock et al. use molecular modeling, knockout mice and cell based studies to show that LIMP-2 also mediates lysosomal cholesterol transport.

During cold stimulation, cholesterol is converted to bile acids in an alternative pathway. The bile acids then alter the microbiota, which in turn promotes more heat generation.

Here, the authors show that short-term consumption of energy-dense diets deficient in fiber, similar to eating patterns for many people today, results in a transient depression of the mucosal and systemic immune systems such that susceptibility to bacterial infection is increased.

Functionalized InAs quantum dots emitting in the short-wavelength infrared spectral region enable functional biomedical imaging at unprecedentedly high spatial resolution, deep penetration and fast acquisition speeds.

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.

During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.

Despite widespread transcription of LncRNA in mammalian systems, their contribution to metabolic homeostasis at the cellular and tissue level remains elusive. Here Pradas-Juni et al. describe a transcription factor–LncRNA pathway that couples hepatocyte nutrient sensing to regulation of glucose metabolism in mice.

Changes in the biosynthesis of fatty acids can influence tissue insulin sensitivity and the development of metabolic diseases. Eissing and colleagues show that de novolipogenesis in liver and adipose tissue is linked to metabolic health in humans and can be modulated by bariatric surgery.

Nanocrystals - such as quantum dots and magnetic nanoparticles - embedded in lipoproteins can be used to image and quantify the kinetics of lipid metabolism in vivo in a non-invasive manner using fluorescence and dynamic magnetic resonance imaging.

A new paper reports that the protein isthmin 1 is secreted by mature adipocytes and triggers a signalling cascade similar to that of insulin. The novel adipokine acts through an unidentified receptor tyrosine kinase and, at pharmacological doses in mice, isthmin 1 ameliorates metabolic disturbances associated with type 2 diabetes mellitus, including hyperglycaemia and liver steatosis.

During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.

Adipocytes respond to environmental cues, such as metabolic stress, by releasing endocrine factors that modulate diverse physiological processes. This Review discusses the metabolic functions of adipose tissue-derived endocrine hormones and highlights how these factors might contribute to cardiometabolic diseases.

Kornfeld and colleagues identify miRNAs that are dysregulated in brown adipose tissue in mouse models of obesity and ageing, and show that miR-328 targets Bace1 to promote brown adipogenesis.