Search

Obesity impairs metabolic flexibility-the capacity to adapt to fluctuating energy demands. Here, authors show that PRMT3 mediates the post-translational adaptation of visceral fat to fasting regulates metabolic flexibility and could be a therapeutic target for obesity.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Thyroid hormones are well known to regulate whole-body energy metabolism, which was believed to occur as a direct effect on individual cells in the periphery. But Antonio Vidal-Puig and his colleagues now show that these thyroid hormone effects on energy regulation are actually indirect, as they regulate AMPK activity in the hypothalamus and thus central signaling to brown adipose tissue in the periphery.

The homeostasis and function of adipose tissue are tightly regulated by immune cells, with macrophages playing a pivotal role. Here the authors show that PpargHIGH macrophages positively enhance brown adipose tissue thermogenesis through GDF15.

The LITMUS consortium provides a resource of rodent MASLD models benchmarked against metabolic, histologic and transcriptomic features that are relevant for human MASLD. The work is useful for selecting relevant rodent models for studying this common disease.

In a recent study, beige adipocytes were derived from the capillaries of human subcutaneous adipose tissue. When implanted into mice, these cells enhanced glucose tolerance, thus providing evidence for their potential therapeutic use.

One UK institute has produced a dozen Nobel laureates and biomedical breakthroughs across the board. How does Cambridge’s Laboratory of Molecular Biology do it? Our study found out.

Here the authors show that lowering IGF-1R levels in endothelial cells improves insulin sensitivity, boosts energy use, and supports beneficial changes in adipose tissue, offering insights into potential treatments for obesity-related metabolic disorders.

Brown adipose tissue (BAT) thermogenesis is an important determinant of organismal energy expenditure in mammals. Here, Whittle et al. report that the protein sLR11 is a negative regulator of BAT activity in mice, repressing thermogenesis by inhibiting BMP/Smad signalling in brown adipocytes.

Regulation of body temperature by the nervous system is essential for physiological function in both health and disease. The immune system also seems to have a crucial role in this process. See Letter p.104

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

During cold exposure, activated brown adipose tissue takes up a large amount of circulating glucose to fuel thermogenesis. Here, the authors show that cold stress enhances the packaging of miR-378a-3p into BAT-derived EVs, which are delivered to the liver and consequently stimulates gluconeogenesis.

Not all individuals with obesity develop cardiometabolic complications. Huang et al. use genome-wide meta-analysis to identify genetic loci associated with lower cardiometabolic risk despite increased adiposity.

Insulin/IGF-1 signalling plays an important role in the regulation of metabolism and ageing. Here the authors show that inactivation of the pathway component PI3K p110α in the adipose tissue of mice produces a beneficial metabolic effect by enhancing β-adrenergic signalling thus energy expenditure.

Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.

Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.

Dietary fatty acids have different effects on human health. Here, the authors show that ingestion of the fatty acid C18:0, but not of C16:0, rapidly leads to fusion of mitochondria and fatty acid oxidation in humans, possibly explaining the health benefits of C18:0.

Activation of brown adipose tissue can ameliorate obesity and diabetes. Here the authors show that chemical inhibition of hyaluronan synthesis by 4‐methylumbelliferone or genetic deletion of hyaluronan synthases 2 and 3 decreases body-weight gain and improves glucose homeostasis by inducing the thermogenic capacity of brown adipose tissue in mice.

Impaired adipocyte insulin signalling characterizes insulin resistance. Here the authors show that the hormone-sensitive lipase can sequester the glucose-responsive transcription factor ChREBP in the cytoplasm, which prevents transcription of its target ELOVL6, resulting in reduced insulin signalling.

Hepatic bone morphogenetic protein 8b expression is shown to be induced in NASH to drive wound healing responses and NASH progression by promoting inflammatory pathways in hepatic stellate cells and, more broadly, in the liver parenchyma.

In mouse studies, metformin treatment results in increased secretion of growth/differentiation factor 15 (GDF15), which prevents weight gain in response to high-fat diet, and GDF15-independent lowering of circulating blood glucose.

Bone is resorbed by osteoclasts, and too much activity by these cells leads to disease, such as osteoporosis. Here Kyoji Ikeda and colleagues show that the combined action of iron uptake and a key transcription factor involved in mitochondrial biogenesis are required for the proper functioning of these cells and that in cases of increased bone loss, iron chelation may be beneficial by inhibiting these cells.

Ruth Loos and colleagues use genome-wide association to identify common variants influencing body fat percentage. Unexpectedly, they show that a body-fat–decreasing allele near IRS1 is associated with an impaired metabolic profile, including increased risk of type 2 diabetes and coronary artery disease.

Enhancing thermogenesis is a promising therapeutic strategy for promoting metabolic health. Here the authors show that adipocyte-secreted BMP8b contributes to optimizing the thermogenic response by remodeling of the neuro-vascular networks in brown and white adipose tissue.

A recent study shows how hyperinsulinaemia in obesity unexpectedly activates the cell cycle of overworked mature adipocytes in a process known as endo-reduplication, which represents a ‘last gasp’ strategy to remain functionally competent. However, this strategy fails and triggers premature senescence and tissue dysfunction.

Genetic analysis in mice selected for leanness has identified thiosulfate sulfurtransferase as a target for the treatment of diabetes.

Bidault et al. find that interleukin-4 activates SREBP1 to promote de novo lipogenesis that consumes NADPH to drive alternative activation of macrophages through the accumulation of reactive oxygen species.

In times of starvation the liver turns into a glucose-producing organ, providing fuel for the brain. The hormonal signals that control this switch in glucose metabolism may converge on a single regulatory molecule.

Mitochondrial uncoupling proteins (UCPs) have long been suspected to have a role in obesity. A study¹ of mice ablated of Ucp2 reveals an unexpected role for the protein in macrophage-mediated immunity. It also supports the notion that the UCP proteins, which uncouple respiration from energy production, might also control the production of reactive oxygen species (ROS).

A high-fat diet can lead to insulin resistance and the development of the metabolic syndrome, a condition associated with diabetes, heart disease and other ailments. A G-protein-coupled receptor on the surface of insulin-secreting cells in the pancreas senses lipids and may promote the metabolic syndrome under high-fat conditions.

The two most common tests for determining metabolic health in mice are the glucose tolerance test (GTT) and insulin tolerance test (ITT). GTTs and ITTs are inexpensive and easy to perform, but how they are conducted and interpreted can radically change their meaning.

This Review discusses the link between metabolic dysfunction-associated steatotic liver disease (MASLD) — a heterogeneous health condition — and hepatic and extrahepatic disease manifestations and provides a comprehensive platform for personalized, holistic management for patients with MASLD.

Mitochondria have essential functions within cells, and their dysfunction is linked to various disorders; here, the fatty acid stearic acid (C18:0), which is a dietary component, and the transferrin receptor (TFR1) are shown to regulate mitochondrial function.