Insulin resistance and type 2 diabetes as allostatic responses to chronic nutrient excess

Challenging dogmas, Prentki et al. propose an alternative paradigm of obesity-related type 2 diabetes, interpreting insulin resistance, reduced glucose-induced insulin secretion, mild hyperglycemia, and glucosuria not as primary pathological abnormalities but as beneficial allostatic responses to nutrient excess. Therapeutic strategies should focus on glucose fate, not blood glucose levels alone.

dlvr.it

Size-Resolved Lipoprotein Fatty Acid Content as a Novel Nuclear Magnetic Resonance-Derived Trait Specifically Associates with Genetic Variants That Control Fatty Acid Metabolism

Population-level nuclear magnetic resonance (NMR)-based lipoprotein profiling is a key tool for investigating dysregulated lipoprotein metabolism and its role in cardiovascular disorders. However, associations with size-resolved lipoprotein composition readouts are difficult to dissect, as these traits are often highly correlated. Derived variables can therefore be more relevant to biological interpretation. Here, we show that the total fatty acid (FA) content of the lipoproteins derived from their lipid headgroup concentrations using the formula FA = 3TG + 2PL + CE strongly correlates (Spearman rho = 0.98) with the independently measured total fatty acid content. This observation is not self-evident since these variables are determined using different portions of the NMR spectrum. Using NMR data acquired on the Nightingale platform for 274,303 UK Biobank (UKB) participants and genetic associations as a readout, we then show that this relationship also holds at the size-resolved lipoprotein level. We identified eight gene loci where the proposed FA variables display a significantly stronger genetic association signal than that of the corresponding lipid headgroup variables. Five of these loci (LIPC, LIPG, PLB1, LPL, and APOC3) have a direct function in FA metabolism. Including computed size-resolved FA variables may therefore improve the biological interpretation of future studies based on Nightingale’s data.

pubs.acs.org

FGF21 reduces ER stress by enhancing the unfolded protein and integrated stress responses through increased sulfide signaling

Grandl et al. reveal a novel physiological role of FGF21 as a hormone of protein folding stress. They show that FGF21 enhances but does not initiate the unfolded protein response and integrated stress response via increased enzymatic sulfide production, thereby improving stress resilience and reducing ER stress.

dlvr.it

The evolving landscape of obesity pharmacotherapy - Nature Reviews Drug Discovery

Incretin-based therapies are transforming the treatment of obesity and related comorbidities. This Review outlines the current landscape of obesity drug development, focusing on glucagon-like peptide ...

nature.com

Why in vivo models of disease remain indispensable

Summary: The call to arms for alternatives to model organisms of disease will fail without ongoing integration with – and validation against – complex animal models and support from the animal modelli...

doi.org

Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain

Lin et al. reveal that FGF21 acts on the hindbrain (nucleus of the solitary tract [NTS] and area postrema [AP]), and not the hypothalamus, to reduce body weight. Specifically, FGF21 signaling to the h...

cell.com

The Expanding Landscape of the Glucagon Signaling Network: mechanisms and outcomes.

Abstract. Glucagon is a peptide hormone mainly secreted by the alpha cells of the pancreatic islets in response to nutritional stimuli. Traditionally recog

academic.oup.com

Inflammatory signalling in diabetic cardiomyopathy: molecular mechanisms and potential therapeutic strategies

Nature Reviews Cardiology - In this Review, De Blasio and Ritchie describe the inflammatory pathways involved in the pathogenesis of diabetic cardiomyopathy and discuss potential strategies to...

rdcu.be

A nutrient-hormone axis pivots an energy trade-off between resting thermogenesis and movement expenditure

The biological reason why mammals increase daily energy expenditure when consuming a protein-dilute diet is currently enigmatic. Recognizing that body…

sciencedirect.com

New approach methodologies: Don’t throw the baby out with the bathwater

The NIH has recently called for expanding use of new approach methodologies (NAMs) to reduce use of animals in research. Arany discusses the need not to forget the irreplaceable aspects of animal research and their fundamental importance to biomedical advancement.

dlvr.it

RFK Jr.'s new food pyramid puts meat, cheese and vegetables at the top

Health Secretary Robert F. Kennedy Jr. has announced new dietary guidelines for Americans focused on promoting whole foods, healthy proteins and fats. And he has "declare[d] war" on added sugar.

npr.org

Neuronal fatty acid oxidation fuels memory after intensive learning in Drosophila - Nature Metabolism

Neurons are shown to use fatty acid β-oxidation as a fuel source for memory formation upon intensive learning in Drosophila, challenging the view that neurons are unable to use fatty acids for energy ...

nature.com

Evolution of taste processing shifts dietary preference - Nature

Calcium imaging of taste neurons and the ventral brain provides insight into evolutionary divergence of food choice in Drosophila species, supporting a role of sensorimotor processing in addition to p...

nature.com

From MRI to Ozempic: breakthroughs that show why fundamental research must be protected

In these financially straitened times, funders must recognize that great discoveries often arise from work that was looking for something completely different.

go.nature.com

HT SpaceM: A high-throughput and reproducible method for small-molecule single-cell metabolomics

Single-cell metabolomics (SCM) can probe metabolic heterogeneity but is hindered by low sensitivity for small molecules, limited scalability, and the lack of standardized frameworks for data analysis....

cell.com

The Most Efficient Traveler Isn’t a Bird or a Fish—It’s You on a Bike

A famous graphic, now updated, compares locomotion in the animal kingdom

scientificamerican.com

GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling

During nutrient deprivation, activation of the protein kinase GCN2 regulates cell survival and metabolic homeostasis. In addition to amino acid stress, GCN2 is activated by a variety of cellular stres...

science.org

A consensus guide to preclinical indirect calorimetry experiments

Nature Metabolism, Published online: 24 September 2025; doi:10.1038/s42255-025-01360-4The 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.

bit.ly

a gold trophy with a laurel wreath around it and the words well done on a gold ribbon

ALT: a gold trophy with a laurel wreath around it and the words well done on a gold ribbon

media.tenor.com

Home | RACMEM

Recent Advances and Controversies in the Measurement of Energy Metabolism

racmem.com

Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice

Loss of lean mass is a potential concern for semaglutide-induced weight loss. This study indicates that semaglutide has unexpected effects on skeletal muscle mass and strength in mice, demonstrating a...

cell.com

Covariation MS uncovers a protein that controls cysteine catabolism - Nature

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

nature.com