Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus.

Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects. SUBJECTS/METHODS: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (18F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects. CONCLUSIONS: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.

Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity.

BACKGROUND/OBJECTIVES: The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass. SUBJECTS/METHODS: We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes. RESULTS: Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls. CONCLUSIONS: In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus.

OBJECTIVE: To determine the value of voxel-based morphometry (VBM) of brain SPECT (single-photon emission computed tomography) images (BSI) in discriminating active central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Forty SLE patients (mean age 33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were screened for the presence of CNS involvement following the American College of Rheumatology (ACR) case definition. Patients with CNS infections, uraemia, diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige) with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the statistical parametric mapping. After normalization, segmentation and smoothing the groups of SLE patients with active and inactive CNS manifestations and healthy volunteers were compared using VBM. Post-processed images were compared voxel-by-voxel using t-test in order to determine differences of intensity between groups. This analysis included grand mean scaling, proportional threshold masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of 32 were taken into consideration. RESULTS: VBM analyses of BSI did not show any differences between SLE patients with inactive CNS involvement and normal controls. However, the group of SLE patients with active CNS involvement had a global hypoperfusion, more intense in the frontal, dorsolateral and medial temporal lobe when compared with SLE patients without CNS involvement (P = 0.001) and healthy volunteers (P = 0.001). CONCLUSION: VBM of BSI is a useful and objective method for detecting perfusion abnormalities in SLE patients, which is indicative of active CNS involvement. However, it is not helpful in differentiating the clinical sub-types of CNS involvement according to the ACR classification.