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Introduction: Diabetes in South Asians is driven primarily by impaired beta-cell function. When challenged with a high-calorie diet, this can result in metabolically unfavourable fat accumulation, which in turn worsens beta-cell function, thus constituting a vicious cycle. The investigators hypothesized that short-term mild-to-moderate weight loss induced by calorie restriction could break the cycle, resulting in significant improvements in beta-cell function. The objective of this study, therefore, was to evaluate the efficacy of a short-term weight loss program on body composition and beta-cell function.
Methods: As part of this quasi-experimental pre-post intervention study, 23 overweight normoglycemic participants underwent a low-calorie dietary intervention (∼1500 kcal/day) for a period of 4 weeks. Beta-cell function and insulin sensitivity were measured with a mixed meal challenge test (oral minimal model of glucose) before and after the intervention period. Changes in anthropometric parameters and body composition were also measured. The study was registered prospectively with the Clinical Trials Registry of India - CTRI/2023/04/051807 (https://ctri.nic.in/).
Results: Among the 23 participants in the study, 21 adhered to the intervention. The average weight loss was 3.5 % with an 11 % reduction in trunk fat mass. Beta-cell function, as measured by disposition index, increased by 128 % on average. Robust linear regression analysis showed that beta-cell function improved by 23 % for 1 % weight loss (P = 0.024).
Conclusion: A short-term mild-to-moderate weight loss in overweight normoglycemic subjects effectively improved their beta-cell function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271622 | PMC |
http://dx.doi.org/10.1016/j.metop.2025.100378 | DOI Listing |
Cell Death Differ
September 2025
Graduate Institute of Physiology, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan, Republic of China.
Peroxisome proliferator-activated receptor alpha (PPARα) is a crucial transcriptional factor that regulates fatty acid β-oxidation and ketogenesis in response to fasting. However, the mechanisms underlying PPARα function remain unclear. This study identified a novel PPARα-binding protein-RING finger protein 128 (RNF128)-that facilitates PPARα polyubiquitination, resulting in the degradation and suppression of PPARα function during fasting.
View Article and Find Full Text PDFNature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFNat Commun
September 2025
Department of Biochemistry, University of Illinois, Urbana-Champaign, IL, USA.
Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq.
View Article and Find Full Text PDFCell Prolif
September 2025
Department of Cardiology & Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The mature mammalian heart has limited ability for self-repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression during postnatal cardiac development. PHGDH overexpression promoted myocardial regeneration and cardiac function in apical resection-operated mice, whereas inhibition by NCT-503 inhibited these processes.
View Article and Find Full Text PDFEur J Pharmacol
September 2025
Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China. Electronic address:
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which autoantibodies cause the immune system to attack and destroy pancreatic β-cells, leading to insufficient insulin production and impaired blood glucose control. T follicular helper (Tfh) cells are recognized as a group of CD4 T cells that help B cells to produce high-affinity antibodies. Our previous research found that oxymatrine (OMT) exhibits excellent immunomodulatory properties on Tfh cells in autoimmune diseases.
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