Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes. While hormones, miRNAs, cytoskeletal proteins, and many other effectors can modulate adipocyte development, the best understood regulators of adipogenesis are the transcription factors that inhibit or promote this process. Ectopic expression and knockdown approaches in cultured cells have been widely used to understand the contribution of transcription factors to adipocyte development, providing a basis for more sophisticated in vivo strategies to examine adipogenesis. To date, over two dozen transcription factors have been shown to play important roles in adipocyte development. These transcription factors belong to several families with many different DNA-binding domains. While peroxisome proliferator-activated receptor gamma (PPARγ) is undoubtedly the most important transcriptional modulator of adipocyte development in all types of adipose tissue, members of the CCAAT/enhancer-binding protein, Krüppel-like transcription factor, signal transducer and activator of transcription, GATA, early B cell factor, and interferon-regulatory factor families also regulate adipogenesis. The importance of PPARγ activity is underscored by several covalent modifications that modulate its activity and its ability to modulate adipocyte development. This review will primarily focus on the transcriptional control of adipogenesis in white fat cells and on the mechanisms involved in this fine-tuned developmental process. © 2017 American Physiological Society. Compr Physiol 7:635-674, 2017.

Oncostatin M (OSM) is a multifunctional gp130 cytokine.Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor ␤ (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. Adipose tissue (AT) 3 plays an important role in the maintenance of systemic metabolic homeostasis. Adipokine production is a critical AT function and is highly regulated in several physiological and pathological conditions, including AT expansion, insulin resistance, obesity, and type 2 diabetes. Obesity is closely associated with a chronic, low grade inflammatory state characterized by macrophage infiltration of AT and subsequent proinflammatory adipokine expression (1, 2). Adipokine modulation has been shown to be a key contributor to the insulin resistance often observed in obesity.Cytokines in the interleukin-6 (IL-6)/gp130 family include IL-6, IL-11, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, and oncostatin M (OSM) (3). The gp130 cytokines regulate several physiological and biological processes (4), and some of these cytokines, namely IL-6 and ciliary neurotrophic factor, have profound effects on metabolism and as such have been previous targets for obesity treatment (5-8). Although originally identified for its ability to inhibit tumorigenesis (9), OSM modulates a host of other biological processes that are cell type-dependent (10). Elevated OSM levels have been observed in a variety of inflammatory diseases in humans, including rheumatoid arthritis and atherosclerosis (11,12). OSM also has important roles in hepatic insulin resistance and steatosis (13), inflammation (14), and cardiomyocyte remodeling (15) and has several well characterized actions in the liver (16 -18). Unlike other gp130 cytokines, OSM has its own specific receptor subunit (OSM receptor ␤; hereafter referred to as OSMR) that heterodimerizes with gp130 to create the functional OSM receptor complex, and this complex is responsible for the majority of OSM effects (19).Adipocytes and AT are highly responsive to OSM (20), and Osmr is highly expressed in AT compared with other tissues (21, 22). Significant induction of both Osm and Osmr expres-* This work was supported in part by National Institutes of Health Grant R01DK052968 (to J. M. S.) and National Institutes of Health Nutrition Obesity Research Centers Grant P30DK072476 entitled "Nutritional Programming: Environmental and Molecular Interactions." The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

STAT5 proteins play a role in adipocyte development and function, but their specific functions are largely unknown. To this end, we used an unbiased MS-based approach to identify novel STAT5-interacting proteins. We observed that STAT5A bound the E1β and E2 subunits of the pyruvate dehydrogenase complex (PDC). Whereas STAT5A typically localizes to the cytosol or nucleus, PDC normally resides within the mitochondrial matrix where it converts pyruvate to acetyl-CoA. We employed affinity purification and immunoblotting to validate the interaction between STAT5A and PDC subunits in murine and human cultured adipocytes, as well as in adipose tissue. We found that multiple PDC subunits interact with hormone-activated STAT5A in a dose- and time-dependent manner that coincides with tyrosine phosphorylation of STAT5. Using subcellular fractionation and immunofluorescence microscopy, we observed that PDC-E2 is present within the adipocyte nucleus where it associates with STAT5A. Because STAT5A is a transcription factor, we used chromatin immunoprecipitation (ChIP) to assess PDC's ability to interact with STAT5 DNA-binding sites. These analyses revealed that PDC-E2 is bound to a STAT5-binding site in the promoter of the STAT5 target gene ytokine-nducible 2-containing protein (). We have demonstrated a compelling interaction between STAT5A and PDC subunits in adipocytes under physiological conditions. There is previous evidence that PDC localizes to cancer cell nuclei where it plays a role in histone acetylation. On the basis of our ChIP data and these previous findings, we hypothesize that PDC may modulate STAT5's ability to regulate gene expression by controlling histone or STAT5 acetylation.

The chow-fed OSMR mice exhibited adipose tissue dysfunction and increased proinflammatory adipokine production. These results suggest that intact adipocyte oncostatin M-OSMR signaling is necessary for adipose tissue immune cell homeostasis.