記述言語：英語   出版者・発行元：FASEB Journal  

As obesity progresses, dynamic tissue remodeling of adipose tissue occurs over time, that is, adipocyte hypertrophy, chronic inflammation, and interstitial fibrosis. Some obese individuals exhibit healthy adipose tissue expansion, characterized by modest inflammation and fibrosis despite adipocyte hypertrophy, resulting in “Metabolically Healthy Obesity (MHO)”. In this study, we investigated the effects of transient weight loss on adipose tissue remodeling during the development of obesity. Male C57BL6/J mice received various types of transient weight loss treatments during diet-induced obesity. A 2-week weight loss intervention during the inflammatory phase promoted healthy adipose tissue expansion, reduced ectopic lipid accumulation, and improved glucose metabolism. In contrast, protocols with shorter duration and delayed intervention, failed to induce MHO. Since serum concentrations of ketone bodies were elevated during weight loss, we examined the effects of hyperketonemia on obesity-induced adipose tissue remodeling. Transient treatment with 1,3-butanediol (BD), which increased serum ketone body concentrations to levels similar to those observed during weight loss, induced healthy adipose tissue expansion and reduced hepatic steatosis even during continuous high-fat diet (HFD) feeding. Ketone bodies effectively suppressed activation of adipose tissue fibroblasts in vivo and in vitro. This study provides evidence that an appropriate dietary intervention can promote healthy adipose tissue expansion in mice, even after the regaining of weight, thereby leading to MHO. As the underlying mechanism, our data revealed a key role for ketone bodies in suppressing activation of adipose tissue fibroblasts. This study paves the way for nutritional approaches to induce MHO.

DOI： 10.1096/fj.202501121R

Open Access

Web of Science

Scopus

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Diabetes  

Recent evidence has shown that adipose tissue eventu-ally develops fibrosis through complex cellular cross talk. Although advances in single-cell transcriptomics have provided new insights into cell diversity during this process, little is known about the interactions among the distinct cell types. In this study, we used single-cell analytical approaches to investigate cell-to-cell communications between macrophages and fibroblasts in the adipose tissue of diet-induced obese mice. Spatial transcriptomics was used to understand local cellular interaction within crown-like structures (CLS), a charac-teristic histological feature of adipose tissue in obesity driving inflammation and fibrosis. Macrophages and fibroblasts were divided into several subclusters that appeared to interact more intensely and complexly with the degree of obesity. Besides previously reported lipid-associated macrophages (LAMs), we found a small sub-cluster expressing macrophage-inducible C-type lectin (Mincle), specifically localizing to CLS. Mincle signaling increased the expression of oncostatin M (Osm), sup-pressing collagen gene expression in adipose tissue fibro-blasts. Consistent with these findings, Osm deficiency in immune cells enhanced obesity-induced adipose tissue fibrosis in vivo. Moreover, OSM expression was positively correlated with MINCLE expression in human adipose tissue during obesity. Our results suggest that Osm se-creted by Mincle-expressing macrophages is involved in dynamic adipose tissue remodeling in the proximity of CLS.

DOI： 10.2337/db24-0762

Open Access

Web of Science

Scopus

PubMed

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.2337/db24-0762

Open Access

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1084/jem.20192230

Open Access

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.12865

Open Access

記述言語：日本語

記述言語：日本語

開催年月日： 2025年3月

開催年月日： 2025年2月

開催年月日： 2024年10月

開催年月日： 2024年3月

開催年月日： 2023年2月

記述言語：英語   会議種別：ポスター発表