Volume 5 Issue 6, June 2023

Many people with obesity and type 2 diabetes achieve remission of their diabetes after Roux-en-Y gastric bypass surgery, but the mechanisms of remission remain disputed. We provide our perspective on competing datasets that point towards this effect being due either entirely to the loss of weight or to weight loss-independent effects.

Inflammation is characterized by cell metabolic reprogramming that can influence the outcome of metabolic syndrome-related diseases such as non-alcoholic fatty liver disease (NAFLD). In this issue, Weiss et al. discover that preventing the production of the immunomodulatory metabolite itaconate increases liver fat accumulation in mouse models of NAFLD and that treatment with itaconate may promote fat oxidation. This study reveals new therapeutic potential for targeting the itaconate metabolic pathway in NAFLD.

Adipogenesis of adipose progenitor cells is considered metabolically beneficial. Two laboratories have simultaneously discovered that adipose progenitors also give rise to structural WNT-regulated adipose tissue-resident (SWAT) cells during adipogenesis to maintain the progenitor pool.

Post-ingestive signals of nutrient availability can drive food reward and neural responses independently of orosensory signals. van Galen et al. demonstrate that brain responses to these post-ingestive signals are impaired in people with obesity

Comparative metabolomic analyses of the guts of healthy colonized versus germ-free mice helped map microbial metabolites across the various intestinal niches. The microbial origin and biochemical processes underlying several metabolites could be inferred, even in areas difficult to access, such as the small intestine.

This Perspective provides a concise overview of the diverse functions of vitamin K in physiology and metabolism, including its recently discovered role in ferroptosis.

This Perspective summarizes the development and clinical efficacy of gut hormone co-agonists for the treatment of diabetes and obesity.

This study shows that the insulinotropic actions of the dual GIPR and GLP-1R agonist, tirzepatide, depend on GIPR, and that tirzepatide has weaker activity at the mouse GIPR than murine GIP.

Alterations in the gut microbiome, as a result of treatment with the anti-diabetic drug acarbose or with antibiotics, are shown to extend healthspan and lifespan in a mouse model of Leigh syndrome.

Anatomically resolved maps of small molecules along the gut of colonized and germ-free mice reveal distinct spatial patterns throughout the gut. These patterns can, in part, be associated with specific microorganisms producing bioactive compounds.

In this study, Weiss, Palmieri et al. show that macrophage-derived itaconate impinges on hepatocyte lipid metabolism. This mechanism participates in the crosstalk of the immune system with hepatocytes during the development of non-alcoholic fatty liver disease.

Single-cell transcriptomic analysis of progenitor cells from human adipose depots reveals an adipogenic and a structural branch of cells, the latter named SWAT cells and shown to display a multipotent phenotype.

Single-cell transcriptomic analysis of human multipotent progenitor cells reveals that upon adipogenic stimulation, Wnt signaling regulates the generation of functional multipotent mesenchymal progenitors, named structural Wnt-regulated adipose tissue resident cells, which maintain the progenitor pool.

Benedetti et al. produce a Cancer Atlas of Metabolic Profiles from 988 metabolomic and transcriptomic tissue profiles across 15 studies to analyse and identify gene–metabolite interactions that transcend cancer types.

The authors show that the protein kinase CaMK1D acts on AgRP/NPY neurons to promote ghrelin’s effects in mediating food intake in male mice.

Brain responses to food are severely diminished in individuals with obesity, and are not improved by 10% body weight loss. These findings point to an important role for the brain in weight regain after weight loss.