58 posts

Suraj Patel shows hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b


Suraj Patel found that while global knockout of IRF3 reduces both liver insulin resistance and steatosis in obesity, hepatocyte-specific knockout of IRF3 in hepatocytes only affects insulin resistance. He was able to track a key target gene of IRF3 down: it’s Ppp2r1b, a component of the PP2A complex which affects AMPK and AKT signaling. This paper demonstrates that inflammation causes insulin resistance in liver by modulating signaling pathways that regulate gluconeogenesis. Read about it in Science Translational Medicine (Hepatic IRF3 Fuels Dysglycemia in Obesity Through Direct Regulation of Ppp2r1b. Science Translational Medicine, 2022; Mar 23;14(637):eabh3831. doi: 10.1126/scitranslmed.abh3831). Suraj’s paper was chosen for the cover image of the current issue Science Translational Medicine, seen here.

Margo Emont spearheads optimization of single nucleus strategies for adipose tissue

The single cell revolution has been going on for a few years, but adipocytes have lagged, because their large size and fragility make them unamenable to traditional whole cell approaches. Our (long and expensive!) optimization of single nucleus strategies for adipose tissue finally pays off. Read our paper (A single cell atlas of human and mouse white adipose tissue. Nature, 2022) in Nature to learn about the diversity of cell types in mouse and human adipose tissue, the discovery of several unique adipocyte subpopulations, and associations between these cells and metabolic diseases like T2D. Cells are featured across visceral and subcutaneous depots, as well as in leanness and obesity. This work was spearheaded by Margo Emont.

A single cell atlas of human and mouse white adipose tissue

Margo P. EmontChristopher JacobsAdam L. EsseneDeepti PantDanielle TenenGeorgia ColleluoriAngelica Di VincenzoAnja M. JørgensenHesam DashtiAdam StefekElizabeth McGonagleSophie StrobelSamantha LaberSaaket AgrawalGregory P. WestcottAmrita KarMolly L. VereggeAnton GulkoHarini SrinivasanZachary KramerEleanna De FilippisErin MerkelJennifer DucieChristopher G. BoydWilliam GourashAnita CourcoulasSamuel J. LinBernard T. LeeDonald MorrisAdam TobiasAmit V. KheraMelina ClaussnitzerTune H. PersAntonio GiordanoOrr AshenbergAviv RegevLinus T. TsaiEvan D. Rosen

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

Nature (2022). https://doi.org/10.1038/s41586-022-04518-2