Nature Metabolism’s First Anniversary

Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of NAD⁺, but how NMN is taken up into cells has not been entirely clear. Here the authors discover a specific NMN transporter, encoded by the Slc12a8 gene, which regulates NMN uptake and cellular NAD⁺ levels in vitro and in the mouse intestine in vivo.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Creatine can be used for thermogenesis in adipocytes. Here Kazak et al. show that creatine uptake is required to sustain this thermogenic pathway. Knockdown of the creatine transporter, CrT, in adipocytes decreases thermogenesis and energy expenditure, whereas creatine supplementation increases energy expenditure in mice fed a high-fat diet.

Proinflammatory activation of liver macrophages and their secretion of proinflammatory cytokines have been linked to obesity. Here Morgantini et al. report a mechanism through which liver macrophages can impair liver metabolism and promote insulin resistance in obesity in the absence of an overt proinflammatory phenotype, through secretion of non-inflammatory factors such as IGFBP7.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Spontaneous control of HIV is linked to the ability of CD8⁺ T cells to eliminate infected CD4⁺ T cells. Here, the authors uncover metabolic differences between HIV-specific, central memory CD8⁺ T cells from spontaneous HIV controllers and antiretrovirally treated non-controllers, and show that in vitro metabolic reprogramming enhances the antiviral response in non-controllers cells.

Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR.

Caused by a compromised lymphatic system, lymphoedema leads to fluid retention and tissue swelling, and is treated primarily with physical therapy. Here the authors present a metabolic approach to reduce lymphoedema by providing the ketone body β-hydroxybutyrate or by feeding ketogenic diet, which increases lymphangiogenesis and reduces fluid retention in mice.

Increased mitochondrial DNA (mtDNA) replication frequency is shown to lead to defects in maintenance of the nuclear genome due to reallocation of nucleotides to mitochondria, challenging the proposed direct role of mtDNA mutations as drivers of cellular and organismal ageing in mammalian progerias.

The anti-diabetic drug metformin is shown to elevate plasma levels of the hormone GDF15. This increase in GDF15 is required for reductions in appetite and body mass, which are known to contribute to the beneficial metabolic effects of the drug.

The gut microbiome has emerged as an important regulator of host physiology and disease, including metabolic diseases. Here Cani et al. provide a broad overview of mechanisms through which the gut microbiota affects metabolic regulation in the host.

Like stem cells, cancer cells can rapidly proliferate but, unlike stem cells, they are mostly locked into a malignant identity. Here, Finley and Intlekofer highlight commonalities in anabolic pathways that support proliferation in cancer and stem cells, and point out unique metabolic features that influence self-renewal and differentiation.