Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase.

Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling

Brown adipose tissue in deep cervical fat of adult ENT patients

Introduction: Until recently, brown adipose tissue (BAT) was only described in newborns. Discovery of thermogenically and metabolically active BAT in adult humans attracted scientists due to its potential to favourably modify the pathophysiology of metabolic diseases. However, most of the available knowledge is based on animal models and imaging data in humans. The aim of our pilot study was to detect and characterize the BAT in the cervical region of adult ENT patients undergoing elective surgery in this anatomical area. Methods: We present a series of first 20 patients in whom subcutaneous and deep cervical fat samples were taken during thyroid or cervical cyst surgery. Tissue was examined histologically for the presence of multilocular adipocytes typical for BAT. Expression of brown (CIDEA, EVA1, UCP1), beige (TMEM26, TBX1, CD137/TNFRSF9) and white (FABP4) adipose tissue genetic markers was determined. Results: BAT markers were detected in fat samples of 9 patients (45%). It was visually identified using light microscopy in 3 patients, while genetic markers were positive in 9 cases. The presence of BAT was not dependent on age or sex, but it negatively correlated with the subjects´ body mass index. Conclusions: BAT is rather unknown tissue to ENT specialists. We provide further evidence of its presence in the deep soft tissue of the neck in adults. Its unique physiological role in energy metabolism is being intensively studied to develop new prevention/treatment strategies for metabolic diseases. As the neck seems to be the major source of BAT in adult human body, it should also raise awareness in our clinical field. Our ongoing research will be focused on its detailed molecular-genetic characterization and factors modulating its physiological function.Supported by: VEGA 2/0180/15Der Erstautor gibt keinen Interessenkonflikt an

Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation.

In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation