Reviews & Analysis

Thermogenic adipocytes can burn lipids and carbohydrates for heat generation. The finding that a primate-specific long non-coding RNA regulates lipolysis and respiration in thermogenic adipocytes reveals a new mechanism controlling thermogenic adipocyte metabolism in humans.

Exposure to high glucose under inflammatory conditions is detrimental to insulin-secreting beta cells in the pancreas. Fu and colleagues describe a metabolic axis that decreases production of the ‘danger molecule’ nitric oxide and improves the survival of beta cells exposed to an inflammatory milieu, thus paving the way to new interventions for diabetes.

Maintaining cellular NAD levels through supplementation with intermediates of NAD synthesis has considerable health benefits. A new study demonstrates that the reduced form of nicotinamide riboside, NRH, can be converted to NAD in a biosynthetic pathway that involves adenosine kinase, thus strongly boosting NAD levels in cells and tissues.

Fructose, a monosaccharide derived from fruits, is primarily consumed in a form combined with glucose as sugar or as a component of high-fructose corn syrup added as a sweetener to processed foods and carbonated beverages. Increased consumption of fructose has emerged as a major contributor to non-alcoholic fatty liver disease, dyslipidaemia, insulin resistance and diabetes. Now Zhao et al. show that hepatic lipid synthesis is increased by fructose metabolism in both the liver and intestine.

Macrophages are required for postinjury skeletal muscle regeneration. A new study reveals that proinflammatory macrophages produce meteorin-like, which promotes muscle stem cell expansion through the Stat3–IGF1 axis and then shifts their inflammatory profile to allow return to homeostasis.

By analysing microbial profiles in three adipose tissue depots and the liver and plasma of morbidly obese individuals, a new study uncovers a unique organ-specific microbial signature, or potential internal ‘tissue microbiota’, in obese people with diabetes.

By introducing a rationally designed metabolic pathway into the genome of Escherichia coli, Kim et al. have re-engineered central carbon metabolism to utilize the one-carbon intermediates formate and methanol for the first time, thus generating a biological platform for sustainable fuel and chemical production.

A recent study by Yuan et al., published in Nature Genetics, demonstrates multidimensional molecular alterations in mitochondrial DNA in human cancers and provides an online catalogue of mitochondrial genomes in many cancer types.

Current pharmacological options for diabetes treatment help patients control blood glucose levels but do not reverse the decline in insulin-secreting β-cells. A new study now shows that a pharmacological combination of insulin and a GLP-1–oestrogen conjugate not only decreases daily insulin requirements but also improves β-cell function.

Inherited deficiencies in oxidative phosphorylation cause severe mitochondrial disease. A recent study in Nature Biotechnology demonstrates that an engineered bifunctional enzyme can rescue the biochemical consequences of mitochondrial dysfunction.

New research in this issue of Nature Metabolism shows how a high-protein diet increases amino acids in blood and atherosclerotic plaques, and in plaque macrophages activates mTOR signalling, suppresses mitophagy and increases apoptosis, thereby exacerbating atherosclerotic-plaque build-up in genetically modified mouse models.

A new study in mice reveals time-dependent effects of a ketogenic diet on resident immune cells in visceral adipose tissue, which have consequences for whole-body metabolic homeostasis.

Extracellular-matrix remodelling contributes to tumour progression, results in intratumoural fibrosis and promotes metastatic behaviour. A new study by Papalazarou et al. now reveals that a pathway involved in ATP supply, the creatine phosphagen system, is a mechanosensitive target during pancreatic cancer invasion.