Search

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Myostatin and activin A are the two primary negative regulators of muscle mass. Blocking these circulating ligands during GLP-1 therapy induces improved body composition through preservation of lean mass and enhanced fat mass loss in obese primates.

Natural hydrogen is generated through chemical and radioactive processes in the Earth’s crust, and could be an important future clean chemical feedstock and energy resource. This Review examines the processes of geological hydrogen generation, migration, accumulation and preservation that enable the development of exploitable reserves.

Extracellular vesicles (EVs) convey inter-organ communication in health and disease. Here, the authors report that adipocyte-derived EVs isolated from insulin-resistant obese but not lean male mice stimulate insulin secretion via the targeted transfer of insulinotropic proteins from adipose tissue to β-cells.

The human microbiota has been implicated in many health-related issues. In this study, the microbiota composition of monozygotic and dizygotic twins and their mothers is examined. Although a core microbiome could not be defined on a phylogenetic level, the data suggests that core functions are conserved.

A study in lean Chinese adults shows that general and central adiposity affects plasma levels of <650 proteins. Moreover, 31 proteins are found to influence levels of adiposity, providing potential targets for developing treatment for obesity.

ApoE is known to be important for lipid nanoparticle function. Here, the authors shows that efficacious coronal ApoE originates from high-density lipoprotein (HDL) particles and, enhances hepatic delivery, making HDL a superior biomarker for lipid nanoparticle potency.

Obesity is a risk factor for cancer. Lynch and colleagues show that obesity alters the cellular metabolism of natural killer cells and decreases their antitumor surveillance and effector responses.

Obesity changes the characteristics of the immune response induced in a mouse model of atopic dermatitis, suggesting therapies that could be used against immune dysregulation in obesity.

Martínez-Álvaro et al. employ metagenomic sequencing to compare the differences in caecum microbiome between lean and genetically obese rabbits exhibiting different levels of intramuscular fat. Lipid aggregation in muscle can be attributed to host genetic interactions with microbial biosynthetic products.

A recent randomised controlled trial demonstrated effectiveness of a remote diet intervention to reduce long covid symptoms in people living with overweight/obesity in the UK. Here, the authors assess the cost-effectiveness of this intervention from the health system and societal perspectives.

Complex phase transformations in β-stabilised titanium alloys can dramatically change their α and β microstructures, providing tailorability for aerospace or biomaterial applications. Here the authors show that Ti-Nb alloys exhibit giant thermal expansions and identify two new pathways that lead to α phase formation.

Bond et al. show that inducible PolG mutation in muscle causes mtDNA damage and muscle wasting. This is driven by the integrated stress response (ISR) and reduction in folate intermediates, linking impaired folate metabolism with ISR/disease induction.

In a first-in-human phase 1/2 study in seven patients with sickle cell disease, autologous hematopoietic stem cell lentiviral gene therapy using reduced-intensity conditioning was considered feasible and safe, achieving >80% reduction in the frequency of vaso-occlusive events.

Many genetic variants have been associated with body size, but the contribution of copy number of rDNA is unknown. Here, the authors explore the association between rDNA copy number and body size in both rats and humans, finding that lower rDNA CN is associated with higher weight and BMI.

Two-step Mendelian randomization, combined with multiple layers of omics evidence, implicates COL6A3-derived endotrophin as a mediator of coronary artery disease risk in the context of obesity.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

Obesity has been reported to promote tumourigenesis and chemoresistance but the underlying mechanisms are not completely understood. Here, the authors show that adipocytes induce Galectin-9 (GAL-9) expression in B-acute lymphoblastic leukaemia (B-ALL) cells which leads to chemoresistance and antibody-mediated blockade of GAL-9 increases survival in preclinical B-ALL murine models.

Analyzing readouts of inflammaging across four cohorts, Franck and colleagues identify strong variation and observe that inflammaging, in its known form, primarily emerges in industrialized—but not nonindustrialized—populations.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

George Kunos and his colleagues show in a rat model that endocannabinoid activation of the Nlrp3 inflammasome in macrophages results in death of pancreatic beta cells, and thus development of type 2 diabetes mellitus. These results suggest that preventing this process might be a therapeutic option for diabetes in the clinic.

Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle.

Energy metabolism is dysregulated in obesity, and some if these changes persist after weight loss and may contribute to weight regain. Here the authors report that a vacuolar-type H⁺ ATPase, ATP6v0a1, is induced in adipocytes during obesity and persists after weight loss, and regulates food intake and weight gain in C. elegans and mice.

Inhibiting the cytosolic enzyme histone deacetylase 6 in the periphery is sufficient to improve leptin sensitivity and metabolic outcomes in diet-induced obese mice.

We find that, relative to central neuropeptide Y, peripheral neuropeptide Y produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.

An appetite-regulating subnetwork in humans involving the lateral hypothalamus and the dorsolateral hippocampus is implicated in obesity and related eating disorders.

To consider the impact of sex on adaptation to space, the European Space Agency initiated VIVALDI dry immersion microgravity simulation in female subjects. Here, the authors show marked deconditioning with 5-day exposure, and propose comprehensive multi-system physiological assessment in 18 healthy women.

Here, Rathnasinghe et al. characterize the pathogenesis of a mouse-adapted SARS-CoV-2 in infected obese and aged mice, and identify mutations that are present in SARS-CoV-2 variants of concern, associated with higher transmissibility.

Tamas Horvath and his colleagues show that in states of obesity activation of the transcription factor PPAR-γ in POMC neurons occurs, resulting in an increase in peroxisome proliferation. This cellular event leads to reduced ROS levels in these cells, decreased neuronal firing and increased food intake. They also show that central pharmacological inhibition of PPAR-γ reverses these effects, suggesting a possible way to combat obesity.

Most cancer patients experience loss of appetite and feelings of illness, which contribute to cancer-related deaths and morbidity. The authors demonstrate that, in mice, activation of a subset of neurons in the parabrachial nucleus mediate cancer-induced anorexia and associated sickness behaviors.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

Tham and Bernardo et al. show that cardiomyocyte-specific knockout of estrogen receptor alpha induces increased adiposity and tissue metabolic alterations specifically in female mice, likely in part due to changes in the proteomic content of the heart-derived extracellular vesicles.

Inhibition of AMPK leads to metabolic perturbations yet how AMPK is inactivated is not fully understood. Here the authors show protein phosphatase 6 subunit SAPS3 is a negative regulator of AMPK and loss of SAPS3 activates AMPK and protects male mice against overnutrition.