Obesity is strongly associated with metabolic diseases, which have become a global health problem. Exploring the underlying mechanism of adipogenesis is crucial for the treatment of excess white fat. Oncogene YBX1 is a multifunctional DNA- and RNA-binding protein that regulates brown adipogenesis. However, the role of YBX1 in white adipogenesis and adipose tissue expansion remains unknown. Here, we showed that YBX1 deficiency inhibited murine and porcine adipocyte differentiation. YBX1 positively regulated adipogenesis through promoting ULK1- and ULK2-mediated autophagy. Mechanistically, we identified YBX1 serves as a 5-methylcytosine (m⁵C)-binding protein directly targeting m⁵C-containingUlk1mRNA by using RNA immunoprecipitation. RNA decay assay further proved that YBX1 upregulated ULK1 expression though stabilizing its mRNA. Meanwhile, YBX1 promotedUlk2transcription and expression as a transcription factor, thereby enhancing autophagy and adipogenesis. Importantly, YBX1 overexpression in white fat enhanced ULK1/ULK2-mediated autophagy and promoted adipose tissue expansion in mice. Collectively, these findings unveil the post-transcriptional and transcriptional mechanism and functional importance of YBX1 in autophagy and adipogenesis regulation, providing an attractive molecular target for therapies of obesity and metabolic diseases.

A potential therapeutic target to curb obesity and diabetes is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role of cyclin dependent kinase inhibitor 2A (Cdkn2a) as a molecular pedal for the beige-to-white transition. Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and male mice confer long-term metabolic protection from diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistically, Cdkn2a promotes the expression and activity of beclin 1 (BECN1) by directly binding to its mRNA and its negative regulator BCL2 like 1 (BCL2L1), activating autophagy and accelerating the beige-to-white transition. Reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a ablation. Furthermore, hyperactive BECN1 alone accelerates the beige-to-white transition in mice and human. Notably, both Cdkn2a and Becn1 exhibit striking positive correlations with adiposity. Hence, blocking Cdkn2a-mediated BECN1 activity holds therapeutic potential to sustain beige adipocytes in treating obesity and related metabolic diseases.

There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it. Mechanistically, the CCL22 receptor, C-C motif chemokine receptor 4 (CCR4), within eosinophils and its downstream focal adhesion kinase/p65/interleukin-4 signaling are essential for CCL22-mediated beige adipocyte formation. Moreover, CCL22 levels are inversely correlated with body weight and fat mass in mice and humans. Acute elevation of CCL22 levels effectively prevents diet-induced body weight and fat gain by enhancing adipose beiging. Together, our data identify the CCL22-CCR4 axis as an essential mediator for LN-controlled adaptive thermogenesis and highlight its potential to combat obesity and its associated complications.

Fermented liquid feed (FLF) is a microbiologically fermented, highly nutritious and easily digestible feed. This study investigated the effects of FLF on growth performance, carcass traits, meat quality, antioxidant capacity, and intestinal microbes of Yuedong black pigs. The pigs were divided into a control group and FLF group. Compared with the control, FLF increased (p < 0.05) the ADG and body weight of Yuedong black pigs. FLF increased (p < 0.05) the loin muscle area, and reduced cooking loss and meat color brightness (L*) of longissimus thoracis. Furthermore, FLF reduced (p < 0.05) the contents of bitter amino acids, including histidine and arginine. The expression of MYH4 (a fast glycolytic fiber gene) and TNNI1 (an inhibitor of muscle contraction) was increased (p < 0.05) in longissimus thoracis from the fermentation group. FLF increased (p < 0.05) the lipogenesis-related gene expression of FABP4, CEBPα, and PPARγ and the protein level of FATP4. Moreover, FLF increased (p < 0.05) serum T-AOC and GPx activity. In addition, FLF improved colonic microbial diversity and increased (p < 0.05) the abundance of Fibrobacterota (Phylum)-degrading cellulose and Lachnospiraceae-AC2044-group (genus)-generating butyric acid. In conclusion, FLF has a broad perspective for improving growth performance, meat quality, antioxidant capacity, and intestinal microbiota composition of Yuedong black pigs.