UCP1 is essential for mitochondrial structural integrity and function in brown adipose tissue

With the recent discovery of functional brown adipose tissue (BAT) in humans, there is a renewed interest in harnessing this thermogenic organ for the therapeutic treatment of diabetes and obesity. BAT activation increases energy expenditure and BAT mitochondria, through the actions of uncoupling protein 1 (UCP1), are integral to this energy wasting process. In response to adrenergic stimulation, UCP1 uncouples the proton pumping actions of the electron transport chain from ATP synthesis releasing the stored chemical energy as heat. While this phenomenon has been intensely investigated, surprisingly little is known about how BAT mitochondria distinctively adapt to the expression and activation of UCP1, which makes up a large percentage of BAT mitochondrial proteome. By taking advantage of UCP1-null animals in combination with bioenergetic profiling and transmission electron microscopy, we provide clear evidence that UCP1 is necessary to maintain mitochondrial structure and function in brown fat. Furthermore, using novel ‘complexomic’ and proteomic profiling we demonstrate that mitochondrial supercomplex formation and stability in BAT requires UCP1. Finally, we show that the loss of UCP1 induces cellular stress, mitochondrial structural alterations and mitochondrial autophagy in an activation dependent manner. Taken together these data suggest that UCP1 is necessary for optimal mitochondrial function and health in brown adipose tissue and call into question any direct mitochondrial mechanism for heat generation in brown fat lacking UCP1

Prevalence of nonpolypoid colorectal neoplasia: an italian multicenter observational study

BACKGROUND AND STUDY AIM: The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology.PATIENTS AND METHODS: This was a multicenter cross-sectional observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers.RESULTS: In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P < 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P < 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001).CONCLUSIONS: NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology