Objective: Fibroblast growth factor 2 (FGF2) has been reported to play divergent roles in white adipogenic differentiation. However, whether it regulates thermogenesis of fat tissues remains largely unknown. Thus, we aimed to investigate the effect of FGF2 on fat thermogenesis and elucidate the underlying mechanisms. Methods: FGF2-KO and wild-type (WT) mice were fed with chow diet and high-fat diet (HFD) for 14 weeks. The brown and white fat mass, thermogenic capability, respiratory exchange ratio, and hepatic fat deposition were determined. In vitro experiments were conducted to compare the thermogenic ability of FGF2-KO- with WT-derived brown and white adipocytes. Exogenous FGF2 was supplemented to in vitro-cultured WT brown and ISO-induced beige adipocytes. The FGFR inhibitor, PPARγ agonist, and PGC-1α expression lentivirus were used, with the aid of technologies including Co-IP, ChIP, and luciferase reporter assay, to elucidate the mechanisms underlying the FGF2 regulation of thermogenesis. Results: FGF2 gene disruption results in increased thermogenic capability in both brown and beige fat, supporting by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential in response to cold exposure. Thus, deletion of FGF2 protects mice from high fat-induced adiposity and hepatic steatosis. Mechanistically, in vitro investigations indicated FGF2 acts in autocrine/paracrine fashions. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression, thereby leading to suppression of UCP1 expression in brown and beige adipocytes. Conclusions: These findings demonstrate that FGF2 is a novel thermogenic regulator, suggesting a viable potential strategy for use of FGF2-selective inhibitors in combat adiposity and associated hepatic steatosis.

Protein succinylation, hepatic metabolism, and liver diseases

As the most prevalent hepatic disorder worldwide, metabolic dysfunction-associated steatotic liver disease (MASLD) afflicts over one-third of the global population, representing a significant public health challenge. The multifactorial pathogenesis of this condition is principally rooted in metabolic dysregulation. It is notable that emerging evidence highlights a critical role for gut microbiota (GM) in disease initiation and progression. This comprehensive review elaborates some representative GM species that influence hepatic lipid metabolism and elucidates the mechanisms through which GM dysbiosis exacerbates MASLD pathogenesis. Importantly, the positive or negative effects of intestinal bacterial communities on MASLD are largely dependent on their special metabolites, such as short chain fatty acids, ethanol, and trimethylamine N-oxide. Current therapeutic strategies targeting GM modulation, including prebiotics, probiotics, fecal microbiota transplantation, specific medicines, and bacteriphages, demonstrate promising efficacy that partially restores microbial equilibrium and mitigates hepatic steatosis. Although limitations still persist in achieving sustained clinical remission, the expanding frontier of microbiome research continues to refine our understanding of host-microbiota crosstalk in MASLD. Future investigations integrating multiple approaches and longitudinal clinical data hold potential to unravel complex microbial networks, paving the way for innovative therapeutic breakthroughs in metabolic liver disease management.