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Thyroid hormones (TH) control brown adipose tissue (BAT) activation and differentiation, but their subsequent homeostatic response following BAT activation remains obscure. This study aimed to investigate the relationship between cold- and capsinoids-induced BAT activation and TH changes between baseline and 2 hours post-intervention. Nineteen healthy subjects underwent 18 F-fluorodeoxyglucose positron-emission tomography ( 18 F-FDG PET) and whole-body calorimetry (WBC) after 2 hours of cold exposure (~14.5 °C) or capsinoids ingestion (12 mg) in a crossover design. Standardized uptake values (SUV-mean) of the region of interest and energy expenditure (EE) were measured. Plasma free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured before and 2 hours after each intervention. Subjects were divided into groups based on the presence (n = 12) or absence (n = 7) of BAT after cold exposure. 12 of 19 subjects were classified as BAT-positive. Subjects with BAT had higher baseline FT3 concentration, baseline FT3/FT4 ratio compared with subjects without BAT. Controlling for body fat percentage, FT3 concentration at baseline was associated with EE change from baseline after cold exposure (P = 0.037) and capsinoids (P = 0.047). Plasma FT4 level significantly increased associated with reciprocal decline in TSH after acute cold exposure and capsinoids independently of subject and treatment status. Circulating FT3 was higher in BAT-positive subjects and was a stronger predictor of EE changes after cold exposure and capsinoids in healthy humans. BAT activation elevates plasma FT4 acutely and may contribute towards augmentation of thermogenesis via a positive feedback response.

The estimation of calories in foods is central in the maintenance of body weight and energy regulation. Conventional laboratory analysis using bomb calorimetry to determine calorie content is expensive and time-consuming. There is a need to explore alternative techniques for calorie estimation that requires less processing and resources. The potential of using near infrared spectroscopy for calorie measurements with Calorie Answer was evaluated in this study. The caloric content of 105 different foods was measured, and compared against values reported on nutrition labels. The average percentage relative standard deviation for triplicate measurements was 1.7% for all foods. The percentage difference between stated and measured calories was modest, at 4.0% for all foods. Stated and measured calorie contents were significantly and highly correlated (R2=0.98, p<0.001). The use of near infrared spectroscopy, using Calorie Answer, is a rapid, reproducible and cost-effective way of measuring calorie content in a diverse range of foods. Its application in many parts of Asia Pacific and other emerging nations will generate much needed information on the calorie content of complex foods consumed by people living in these regions.

Abstract Background Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. Objective Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. Design Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. Main Outcome Measures Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). Results Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, −404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Conclusion Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. Highlights A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves’ disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12–24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18 F-fluorodeoxyglucose ( 18 F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health. Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score. Clinical Trial Registration : The trial was registered at clinicaltrials.gov as NCT03531879.

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.

Correspondence to Dr Melvin Khee Shing Leow, Singapore Institute for Clinical Sciences, Singapore 117609, Singapore; melvin_leow@sics.a-star.edu.sg Introduction In the routine evaluation of the thyroid, imaging is often a useful modality, which gives anatomical and functional characteristics that can aid diagnosis. Thyroid ultrasonography is the principal imaging modality in this regard, whereas CT, MRI and PET scanning are much less frequently ordered for thyroid assessment through thyroid lesions are often discovered via such advanced imaging modalities as incidental findings.1 Unlike radiologists, most physicians tend to be unfamiliar with radiological features of thyroid disorders detected via these latter forms of scanning.2 Case description A 25-year-old woman who was otherwise overtly healthy and asymptomatic without any history of medical illnesses or chronic medications had volunteered for a research study on brown fat. Conclusion The rising prevalence of autoimmune thyroiditis coupled with an increasing use of 18F-FDG-PET scanning for various indications will continue to generate such incidental findings as highlighted by our case.3 4 Although diffusely increased 18F-FDG thyroid uptake is observed in hyperthyroidism such as Graves’ disease, physicians should recognise that diffusely increased 18F-FDG thyroid uptake can also be due to Hashimoto thyroiditis,5 which contrasts starkly with diminished 99mTc/131I uptake typical of subacute thyroiditis6 and that must be differentiated from analogous scintigraphic features of Graves’ disease characterised by diffusely accentuated 99mTc/131I and 18F-FDG uptake.

The difference between fat saturation on postprandial hormone responses and acute appetite control is not well understood. The aim of this study was to compare the postprandial ghrelin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP1) response and subjective appetite responses after isoenergetic high-fat meals rich in either monounsaturated (MUFAs) or polyunsaturated fatty acids (PUFAs) in healthy Chinese males. A randomized, controlled, single-blinded crossover study was conducted in 13 healthy Chinese men. Two high-fat meals (64% of energy) rich in MUFAs or PUFAs were tested. Total ghrelin, GIP and active GLP1 and visual analog scale (VAS) were measured over 4 h. Ghrelin was reduced greater after MUFA compared to PUFA at the beginning of the meal (at 30 and 60 min) and was significantly negatively correlated with subjective VAS for preoccupation for both MUFA and PUFA meals. No significant difference for ghrelin 240 min incremental area under the curve (iAUCs) were found. MUFA induced higher GIP response than PUFA. GIP was associated with all the VAS measurements except preoccupation for MUFA meal. No difference was found for GLP1 between two meals, nor was GLP1 associated with VAS. In conclusion, the results demonstrate that ghrelin, GIP and VAS respond differently to MUFA and PUFA meals. Ghrelin and GIP, but not GLP1, were associated with acute appetite control, especially after MUFA meal.