Highlights d Beige fat progenitors are marked by cell surface proteins, PDGFRa, Sca1, and CD81 d Beige APC proliferation is regulated by temperature, genetic background, and aging d CD81 mediates integrin-FAK signaling in response to irisin d CD81 loss causes obesity, insulin resistance, and adipose tissue inflammation

Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor β-dependent pro-fibrosis genes by recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.

Plant-derived lignans, consumed daily by most individuals, are thought to protect against cancer and other diseases 1 ; however, their bioactivity requires gut bacterial conversion to enterolignans 2. Here, we dissect a four-species bacterial consortium sufficient for all five reactions in this pathway. A single enzyme (benzyl ether reductase; ber), was sufficient for the first two biotransformations, variable between strains of Eggerthella lenta, critical for enterolignan Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Metabolic complications relating to complex effects of viral and immune-mediated mechanisms are now a focus of clinical care among persons living with human immunodeficiency virus (PLHIV), and obesity is emerging as a critical problem. To address knowledge gaps, the US National Institutes of Health sponsored a symposium in May 2018 entitled “Obesity and Fat Metabolism in HIV-infected Individuals.” Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PLHIV. Fibrotic subcutaneous adipose tissue is metabolically dysfunctional and loses its capacity to expand, leading to fat redistribution, including visceral obesity and ectopic fat accumulation, promoting insulin resistance. Viral proteins, including viral protein R and negative regulatory factor, have effects on adipogenic pathways and cellular metabolism in resident macrophages and T cells. HIV also affects immune cell trafficking into the adipose compartments, with effects on adipogenesis, lipolysis, and ectopic fat accumulation. Key cellular metabolic functions are likely to be affected in PLHIV by gut-derived cytokines and altered microbiota. There are limited strategies to reduce obesity specifically in PLHIV. Enhancing our understanding of critical pathogenic mechanisms will enable the development of novel therapeutics that may normalize adipose tissue function and distribution, reduce inflammation, and improve insulin sensitivity in PLHIV.

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Our findings dissociate BMI from adiposity in Chinese individuals and instead highlight SCAT fibrosis as a process linked to visceral adiposity and insulin resistance in this group.

Serial analysis of gene expression (SAGE) provides a global analysis platform for profiling mRNA populations present in cells of interest without the constraint of gene selection and the ambiguous nature of data obtained. However, most of the reports on SAGE and germ cell development are limited to descriptive analyses. Here, we report a series of bioinformatic analyses using recently published SAGE data on the transcriptome of mouse type A spermatogonia (Spga), pachytene spermatocytes (Spcy), and round spermatids (Sptd). Tags with a total count of > or =20 in three SAGE libraries were examined. Our aim was to identify and discover potential transcriptional regulators and pathways involved at different stages of spermatogenesis. Unsupervised hierarchical clustering based on tag expression and Gene Ontology analysis were applied to identify genes and biological processes overrepresented at a particular stage of development. The 5' cis-regulatory elements were examined for common regulators in different functional clusters. Potential biological networks were also constructed to reveal the link between the gene candidates. Biological pathways related to the three germ cell stages were constructed. A number of known transcription regulators in spermatogenesis, including NF-kappaB, SP1, AP-1, and EGR, were identified. Novel promoter elements such as the E box in Spga-specific genes, GATA in Spcy-specific genes, and GKLF in Sptd-specific genes were also observed. Taken together, our approach is reliable and provides a foundation for the generation of novel biological hypotheses for studying spermatogenesis.

Authorship note: PCM and JTC are co-first authors. Conflict of interest: MSG holds stock in Viacyte Inc. and Encellin Inc. MA holds stock in Medtronic and Merck. SAO is a scientific co-founder of, equity holder in, and consultant for OptiKira LLC.