Study On The Related Factors And Mechanism Of Brown Adipose Tissue Activation In Chinese Adults

Obesity has become a serious threat in public health worldwide. Substantial epidemiologic evidence indicates that obesity is associated with hypertension, coronary artery disease, cerebrovascular accident, type 2 diabetes, dyslipidemia and cancers. Recent studies have shown active brown adipose tissue (aBAT) is present in adults and may play important roles in regulating energy homeostasis. This may be a potential target for the therapy of obesity and related metabolic disturbance.Very little is known about the prevalence of aBAT in Chinese adults. Almost all human cohort studies were done in patients for cancer surveillance and thus may not represent healthy subjects. And all studies just analyzed baseline characteristics such as sex, age, body mass index (BMI), history of cancer and fasting plasma gluscose (FPG), but the potential factors such as smoking, drinking, exercise and thyroid diseases, which are related to norepinephrine and thyroid hormone secretion, haven't been included. The relationship between BAT activity, thyroid function and brain metabolism in adults are unclear. So we observed the characteristics of distinct adult cohorts with different BAT activities and thyroid functions, and explored the aBAT related factors and its central regulation mechanism. Our results may contribute to the foundation of future research in this area.Part I The Prevalence and Related Factors of Active Brown Adipose Tissue in Chinese AdultsObjective:To evaluate the difference between subjects for cancer surveillance and subjects for medical check-up, and determined the impact of life style and other parameters on aBAT.Methods:We analyzed 31,088 subjects who performed fluorine-18-fluorodeoxyglucose positron-emission tomography and computed tomography (18F-FDG PET-CT) from July 1,2006 to June 30,2010 at Huashan hospital and examined the characteristics of subjects with aBAT. Results:Active BAT predominantly exists from anterior neck to the thorax, and was seen in 410 of the 31,088 subjects (1.32%), which is lower than previous finding (5.37%). Among cancer surveillance patients, aBAT was found in 146 of 14,389 (1.01%), while it was 264 of 16,699 (1.58%, p<0.05) in medical check-up group. The prevalence of aBAT was higher in women (2.36%[273 of 11570]) than in men (0.70%[137 of 19518], P<0.0001). In both groups, the prevalence of aBAT is higher in women than men (1.59% vs 0.61%,3.16% vs 0.77%, P<0.0001, respectively). In univariate analyses of cancer surveillance group, aBAT was most frequently detected in women (P=0.0005), patients in the bottom third for age (<39.7 years, P=0.0077), the least obese patients (P<0.0001), and those who had never smoked, less drinking, moderate exercise and no fatty liver (P<0.0001, P=0.0015, P=0.0309 and P=0.0003, respectively). The univariate analyses of medical check-up group showed the same results except for exercise (P=0.1937). In age- and sex- adjusted multivariate analyses, BMI, smoking and exercise in the cancer surveillance group remained significant. BMI, smoking and thyroid hypermetabolism in medical check-up group remained significant.Conclusion:In Chinese adults, the prevalence of aBAT is 1.32% and cancer patients have lower prevalence than non-cancer subjects. It is correlated with BMI, smoking, exercise and thyroid diseases besides sex, age and temperature, suggesting the potential role in adult metabolism.Part?The Effects of Thyroid Hormones on Glucose Metabolism of Brown Adipose Tissue and Muscle in Chinese adult humansObjective:The objective of this study was to investigate, for the first time, the effects of thyroid hormones on glucose metabolism of BAT and other organs in Hyperthyroidism.Methods:Ten Graves'disease-caused hyperthyroid patients who were newly diagnosed and untreated were included at our institution. Putative brown-adipose-tissue activity was determined by the integrated 18F-FDG PET-CT. All hyperthyroid patients treated with Methimazole were followed up when the symptoms had disappeared and the thyroid hormone levels were back to normal range within mean seventy-seven days. One of them was withdrawn because of drug allergy. Meanwhile, we studied a group of forty-eight BAT-positive healthy subjects by PET-CT scan, and forty-eight BAT-negative controls on the same scan day.Results:No hyperthyroid patient had active brown adipose tissue identified by PET-CT, except one showed active BAT after anti-thyroid therapy. The free triiodothyronine (FT3)(P=0.003) and free thyroxine (FT4)(P<0.001) were significantly lower in 48 BAT-positive subjects than BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of FDG in skeletal muscles before medical treatment. The standardized uptake value (SUV) was substantially decreased after treatment (P(?)0.001).Conclusion:The higher than normal circulating thyroid hormone levels increased the uptake of FDG in skeletal muscles significantly, but not in BAT, suggesting the increased obligatory thermogenesis of muscles may limit BAT activity in adult humans.Part?Study on the Relationship between Brown Adipose Tissue Activity and Brain Metabolism in Chinese AdultsObjective:To observe the relationship between BAT activity and brain function before and after warm exposure, and assess the feedback regulation between BAT and brain.Methods:Relative regional cerebral glucose metabolism was compared between 15 healthy subjects with activated BAT and 30 healthy controls without activated BAT using brain fluorodeoxyglucose PET scan. A follow-up PET scan was performed to assess metabolic changes of the brain when BAT was disappeared by warm exposure.Results:Compared to controls, BAT-positive subjects exhibited lower activity in the inferior parietal lobule, limbic system and frontal lobe, and higher activity in the precuneus before warm exposure. Compared with the BAT elimination status, subjects with activated BAT showed a decreased metabolism in the parietal lobe, frontal lobe, culmen, cingulated gyrus and sub-lobar; and an increased metabolism in the temporal lobe, parahippocampal and posterior cingulate. Compared to controls, BAT-positive subjects with BAT elimination had significant hypometabolic areas in the temporal lobe and limbic lobe, and hypermetabolic areas in the parietal lobe and cuneus.Conclusion:The differences of regional cerebral glucose metabolism are related to BAT activities in BAT-positive subjects, and some of them can be changed following warm exposure. Brain responses are active in modulating metabolic function of the BAT activity.