Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat–like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition. Mice genetically deficient in Park2 showed reduced mitochondrial degradation and retained thermogenic beige adipocytes even after the withdrawal of external stimuli. Norepinephrine signaling through the PKA pathway inhibited the recruitment of Parkin protein to mitochondria in beige adipocytes. However, mitochondrial proton uncoupling by uncoupling protein 1 (UCP1) was dispensable for Parkin recruitment and beige adipocyte maintenance. These results suggest a physiological mechanism by which external cues control mitochondrial homeostasis in thermogenic fat cells through mitophagy.

Adipose is a key tissue regulating energy homeostasis. In states of obesity, caloric intake exceeds energy expenditure, thereby accelerating lipid accumulation with ongoing extracellular matrix (ECM) remodeling. Excess deposition of lipids and expansion of adipocytes potentially decrease ECM flexibility with local hypoxia and inflammation. Hypoxia and chronic low-grade inflammation accelerate the development of adipose tissue fibrosis and related metabolic dysfunctions. Recent research investigated that some cytokines and proteins are functional in regulating energy homeostasis, meanwhile, are potential targets to fight against adipose tissue fibrosis and insulin resistance. In this review, we focused on the regulatory mechanisms and mediators in remodeling of adipose tissue fibrosis, along with their relevance to clinical manifestations.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by chronic inflammation and pathological lung remodeling driven by excessive extracellular matrix deposition. While the flavonol quercetin exhibits established anti-inflammatory and antioxidant properties, its therapeutic mechanisms against IPF—particularly regarding epithelial-mesenchymal transition (EMT) and inflammation regulation via the follistatin-like 1 (FSTL1)/nuclear factor kappa B (NF-κB) axis—remain incompletely elucidated. This study therefore investigates quercetin’s capacity to mitigate pulmonary fibrosis through targeted modulation of the FSTL1/NF-κB pathway.Methods: A bleomycin (BLM)-induced pulmonary fibrosis mouse model and Transforming Growth Factor Beta 1 (TGF-β1)-induced EMT models in A549 and BEAS-2B cells were employed. The therapeutic effects of quercetin were assessed through H&E, Masson, Sirius red staining, immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of FSTL1 and NF-κB signaling in the anti-fibrotic effects of quercetin was evaluated using FSTL1 knockdown.Results: In vivo studies have shown that BLM-induced pulmonary fibrosis and inflammation significantly increased the deposition of extracellular matrix and the levels of interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6), all of which were markedly reduced by quercetin administration. In vitro experiments revealed that quercetin suppressed TGF-β1-induced EMT and inflammation. Importantly, FSTL1 knockdown diminished the anti-inflammatory and anti-EMT effects of quercetin.Conclusion: Quercetin exerts its protective effects against pulmonary fibrosis by suppressing FSTL1 expression and modulating the NF-κB signaling pathway, thereby inhibiting both inflammation and EMT process.

Individual cell types vary enormously in the amount of different organelles they contain. One such organelle is the mitochondrion. Understanding how mitochondrial levels are controlled is essential since so many disease states seem to involve mitochondrial function. The beige adipocyte is an inducible form of adipocyte that emerges in response to cold exposure and some other external stimuli. To perform its thermogenic function, its level of mitochondria increases dramatically. If the stimuli are removed the mitochondrial levels return to base line. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through mitophagy-mediated mitochondrial degradation. The beige cell is therefore a dynamic model for studying the mechanism of mitochondrial biogenesis and degradation.

Calorie restriction (CR) and exercise training (EX) are two critical lifestyle interventions for the prevention and treatment of metabolic diseases, such as obesity and diabetes. Brown adipose tissue (BAT) and skeletal muscle are two important organs for the generation of heat. Here, we undertook detailed transcriptional profiling of these two thermogenic tissues from mice treated subjected to CR and/or EX. We found transcriptional reprogramming of BAT and skeletal muscle as a result of CR but little from EX. Consistent with this, CR induced alterations in the expression of genes encoding adipokines and myokines in BAT and skeletal muscle, respectively. Deconvolution analysis showed differences in the subpopulations of myogenic cells, mesothelial cells and endogenic cells in BAT and in the subpopulations of satellite cells, immune cells and endothelial cells in skeletal muscle as a result of CR or EX. NicheNet analysis, exploring potential inter-organ communication, indicated that BAT and skeletal muscle could mutually regulate their fatty acid metabolism and thermogenesis through ligands and receptors. These data comprise an extensive resource for the study of thermogenic tissue molecular responses to CR and/or EX in a healthy state.