The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men.
- 作者列表："Nahon KJ","Janssen LGM","SardjoeMishre ASD","Bilsen MP","van der Eijk JA","Botani K","Overduin LA","Ruiz JR","Burakiewicz J","Dzyubachyk O","Webb AG","Kan HE","Berbée JFP","van Klinken JB","van Dijk KW","van Weeghel M","Vaz FM","Coskun T","Jazet IM","Kooijman S","Martinez-Tellez B","Boon MR","Rensen PCN
AIMS:To compare the effects of cold exposure and the β3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids. MATERIAL AND METHODS:Ten lean Dutch South Asian (age 18-30 years; BMI 18-25 kg/m2 ) and ten age- and BMI-matched Europid men participated in a randomized, double-blinded, cross-over study consisting of three interventions; short-term (approx. 2 hours) cold exposure, mirabegron (200 mg one dose p.o.) and placebo. Before and after each intervention, we performed lipidomic analysis in serum, assessed resting energy expenditure (REE) and skin temperature, and measured BAT fat fraction by MRI. RESULTS:In both ethnicities, cold exposure increased levels of many serum lipid species, whereas mirabegron only increased free fatty acids. Cold exposure increased lipid oxidation in both ethnicities, while mirabegron increased lipid oxidation in Europids only. Cold exposure and mirabegron enhanced supraclavicular skin temperature in both ethnicities. Cold exposure decreased BAT fat fraction in both ethnicities. After combination of data from both ethnicities, mirabegron decreased BAT fat fraction compared to placebo. CONCLUSIONS:In South Asians and Europids, cold exposure and mirabegron induced beneficial metabolic effects. When combining both ethnicities, cold exposure and mirabegron increased REE and lipid oxidation, coinciding with a higher supraclavicular skin temperature and lower BAT fat fraction. This article is protected by copyright. All rights reserved.
目的: 比较寒冷暴露和 β3 肾上腺素能受体激动剂 mirabegron 对南亚人和欧洲人群血浆脂质、能量消耗和棕色脂肪组织 (BAT) 活性的影响。 材料和方法: 10 名瘦荷兰南亚人 (年龄 18-30 岁; BMI 18-25千克/m2) 和 10 名年龄和 BMI 匹配的欧洲男性参加了一项随机试验,双盲，交叉研究，包括三个干预措施; 短期 (约。2 小时) 冷暴露，mirabegron (200 mg 一次剂量 p.o.) 和安慰剂。每次干预前后，我们进行血清脂质组学分析，评估静息能量消耗 (REE) 和皮肤温度，并通过 MRI 测量 BAT 脂肪分数。 结果: 在两个种族中，冷暴露增加了许多血清脂质物种的水平，而 mirabegron 只增加了游离脂肪酸。冷暴露增加了两个种族的脂质氧化，而 mirabegroon 仅增加了 Europids 的脂质氧化。寒冷暴露和 mirabegron 增强两个种族的锁骨上皮肤温度。冷暴露降低了两个种族的蝙蝠脂肪分数。在合并来自两个种族的数据后，与安慰剂相比，mirabegron 降低了 BAT 脂肪分数。 结论: 在南亚人和欧洲人群中，冷暴露和 mirabegron 诱导了有益的代谢效应。当结合两个种族时，冷暴露和 mirabegron 增加了 REE 和脂质氧化，同时锁骨上皮肤温度较高，蝙蝠脂肪分数较低。本文受版权保护。保留所有权利。
METHODS:BACKGROUND:Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS:In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS:Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day , 1.32 (0.40) g kg day ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg day , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS:Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.
METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.
METHODS:OBJECTIVE:Postprandial dyslipidemia is a common feature of insulin resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. While bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Approach and Results: Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and with deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA effects (but not DCA) were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the anti-diabetic hormone glucagon-like peptide-1 (GLP-1). While the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate limiting enzyme for bile acid synthesis. CONCLUSIONS:Bile acid signaling may be an important mechanism of controlling dietary lipid absorption and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.