bims-mimead 2025-01-19 papers

Issue of 2025–01–19
six papers selected by
Rachel M. Handy, University of Guelph

Elife. 2025 Jan 13. pii: RP97981. [Epub ahead of print]13

Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity.

Jisun So, Olivia Strobel, Jamie Wann, Kyungchan Kim, Avishek Paul, Dominic J Acri, Luke C Dabin, Jungsu Kim, Gang Peng, Hyun Cheol Roh.

Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.

Keywords: adipocytes; cell biology; genetics; genomics; mouse; obesity; snRNA-seq

DOI: https://doi.org/10.7554/eLife.97981

Am J Physiol Endocrinol Metab. 2025 Jan 17.

Proteomic Profiling Reveals Alterations in Metabolic and Cellular Pathways in Severe Obesity and Following Metabolic Bariatric Surgery.

Prince Dadson, Miikka-Juhani Honka, Tomi Suomi, P A Nidhina Haridas, Anne Rokka, Senthil Palani, Elena Goltseva, Ning Wang, Anne Roivainen, Paulina Salminen, Peter James, Vesa M Olkkonen, Laura L Elo, Pirjo Nuutila.

In this study, we investigated the impact of bariatric surgery on the adipose proteome to better understand the metabolic and cellular mechanisms underlying weight loss following the procedure. A total of 46 patients with severe obesity were included, with samples collected both before and after bariatric surgery. Additionally, 15 healthy, non-obese individuals who did not undergo surgery served as controls and were studied once. We utilized quantitative liquid chromatography tandem mass spectrometry analysis to conduct a large-scale proteomic study on abdominal subcutaneous biopsies obtained from the study participants. Our proteomic profiling revealed that among the 2254 compared proteins, 46 were upregulated, and 34 were downregulated 6 months post-surgery compared to baseline (FDR < 0.01). We observed a downregulation of proteins associated with mitochondrial integrity, amino acid catabolism, and lipid metabolism in the patients with severe obesity compared to the controls. Bariatric surgery was associated with an upregulation in pathways related to mitochondrial function, protein synthesis, folding and trafficking, actin cytoskeleton regulation, and DNA binding and repair. These findings emphasize the significant changes in metabolic and cellular pathways following bariatric surgery, highlighting the potential mechanisms underlying the observed health improvements post-bariatric surgery. The data provided alongside this paper will serve as a valuable resource for the development of targeted therapeutic strategies for obesity and related metabolic complications.

Keywords: Adipose tissue; Bariatric surgery; Metabolic and Cellular Pathways; Obesity; Proteomics

DOI: https://doi.org/10.1152/ajpendo.00220.2024

Sci Rep. 2025 Jan 15. 15(1): 1999

A mediating role of visceral adipose tissue on the association of health behaviours and metabolic inflammation in menopause: a population-based cross-sectional study.

Hannamari Lankila, Tiia Kekäläinen, Enni-Maria Hietavala, Eija K Laakkonen.

Fat distribution changes with advancing menopause, which predisposes to metabolic inflammation. However, it remains unclear, how health behaviours, including sleeping, eating and physical activity, or their combinations contribute to metabolic inflammation caused by visceral adipose tissue (VAT). The aim of the present study was to examine whether health behaviours are associated with metabolic inflammation and whether VAT mediates these associations in menopausal women. This cross-sectional study consisted of a sample of middle-aged women (n = 124). Health behaviours were assessed by self-report questionnaire with measures of sleeping, eating (Eating Disorder Examination Questionnaire, EDE-Q), and physical activity behaviours. Metabolic inflammation was measured using GlycA, a composite biomarker of inflammation, and bioimpedance device was used to assess VAT. Structural equation modelling was used to examine the direct and indirect associations of health behaviours with inflammation, as well as the moderation effect of health behaviours on VAT and metabolic inflammation. VAT was directly associated with inflammation. Two indirect pathways were found: eating and physical activity behaviours were both inversely associated with inflammation through VAT, whereas sleeping behaviour was not. Physical activity moderated the association between VAT and metabolic inflammation. The association was stronger in those who were physically less active. Furthermore, eating behaviour and physical activity had an interaction on VAT. Physical activity was negatively associated with VAT among women with normal eating behaviour, but the association was less clear among women with features of disordered eating behaviour. It is possible to impede the menopausal shift to adverse visceral adiposity through increased physical activity and further decrease the risk of metabolic inflammation in menopausal women. The present study offers potential hypotheses for future longitudinal research.

Keywords: Dimensions of sleep; Eating disorder examination questionnaire; Inflammatory biomarker; Menopause; Physical inactivity; Visceral fat

DOI: https://doi.org/10.1038/s41598-025-85134-8

STAR Protoc. 2025 Jan 14. pii: S2666-1667(24)00502-1. [Epub ahead of print]6(1): 103337

Protocol for inducing beige adipocytes in white adipose tissue of mouse using cold exposure and CL316,243 injection.

Yalan Wu, Chenguang Wang, Xiao Yu Tian.

White adipose tissue (WAT) beiging holds significant therapeutic potential for combating obesity. Here, we present a protocol for inducing beige WAT in mice using both cold exposure and CL316,243 treatment. We describe steps for intraperitoneal injection, and subcutaneous WAT (sWAT) isolation, dissection, and fixation. We then detail procedures for histology, whole-mount immunofluorescence (IF) staining, and extracting RNA and protein. This protocol can be used for subsequent analysis to explore the mechanisms governing beige WAT induction in experimental settings, particularly the evaluation of angiogenesis. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Keywords: Cell Biology; Metabolism; Model Organisms

DOI: https://doi.org/10.1016/j.xpro.2024.103337

Lancet Diabetes Endocrinol. 2025 Jan 13. pii: S2213-8587(24)00339-5. [Epub ahead of print]

Dissection of type 2 diabetes: a genetic perspective.

Amélie Bonnefond, Jose C Florez, Ruth J F Loos, Philippe Froguel.

Diabetes is a leading cause of global mortality and disability, and its economic burden is substantial. This Review focuses on type 2 diabetes, which makes up 90-95% of all diabetes cases. Type 2 diabetes involves a progressive loss of insulin secretion often alongside insulin resistance and metabolic syndrome. Although obesity and a sedentary lifestyle are considerable contributors, research over the last 25 years has shown that type 2 diabetes develops on a predisposing genetic background, with family and twin studies indicating considerable heritability (ie, 31-72%). This Review explores type 2 diabetes from a genetic perspective, highlighting insights into its pathophysiology and the implications for precision medicine. More specifically, the traditional understanding of type 2 diabetes genetics has focused on a dichotomy between monogenic and polygenic forms. However, emerging evidence suggests a continuum that includes monogenic, oligogenic, and polygenic contributions, revealing their complementary roles in type 2 diabetes pathophysiology. Recent genetic studies provide deeper insights into disease mechanisms and pave the way for precision medicine approaches that could transform type 2 diabetes management. Additionally, the effect of environmental factors on type 2 diabetes, particularly from epigenetic modifications, adds another layer of complexity to understanding and addressing this multifaceted disease.

DOI: https://doi.org/10.1016/S2213-8587(24)00339-5

J Endocr Soc. 2025 Jan 06. 9(2): bvae224

Central Downregulation of S-Resistin Alleviates Inflammation in EWAT and Liver and Prevents Adipocyte Hypertrophy.

María Rodríguez, Eduardo Moltó, Rosario Serrano, Jorge Diaz-Rullo, Iván Parralejo, Diego Muñoz, Rosa María Andreu, Jennifer Seco, Nilda Gallardo, Antonio Andrés, Carmen Arribas, Cristina Pintado.

The hypothalamus integrates peripheral signals and modulates food intake and energy expenditure by regulating the metabolic function of peripheral tissues, including the liver and adipose tissue. In a previous study, we demonstrated that s-resistin, an intracellular resistin isoform highly expressed in the hypothalamus and upregulated during aging, is important in the central control of energy homeostasis, affecting mainly the peripheral response to insulin by still unknown mechanisms. Herein, using an intracerebroventricular injection of a specific lentiviral RNAi against s-resistin, we assessed, in the Wistar rat, the effects of central s-resistin downregulation on the expression and phosphorylation levels of intermediates involved in insulin signaling and the inflammatory response in epididymal white adipose tissue (eWAT) and liver. Additionally, we studied the imbalance of eWAT hypertrophy/hyperplasia remodeling. Our results indicate that central downregulation of s-resistin regulates insulin signaling cascade in a tissue-specific manner, reduces the inflammatory status both in the liver and eWAT, and prevents eWAT hypertrophy. Taken together, our results highlight the pivotal role of central s-resistin in maintaining metabolic homeostasis in AT and the liver. This suggests a direct association between its function and the modulation of the inflammatory response in these tissues.

Keywords: central-s-resistin; hypertrophy; inflammation; insulin-resistance; resistin

DOI: https://doi.org/10.1210/jendso/bvae224