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      Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight

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      The Proceedings of the Nutrition Society
      Cambridge University Press
      The 13th European Nutrition Conference (FENS 2019)
      15–18 October 2019
      Brown adipose tissue, Browning, Energy expenditure, Phytochemicals, Weight management, AR, adrenergic receptor, BAT, brown adipose tissue, BBR, berberine, BW, body weight, CAP, capsaicin, COMT, catechol-O-methyltransferase, EE, energy expenditure, EGCG, (−)-epigallocatechin gallate, E2, 17β-oestradiol, ER, estrogen receptor, FGF21, fibroblast growth factor 21, HFD, high fat diet, LSI, lifestyle intervention, OPE, onion peel extract, PGC1α, PPARγ co-activator 1α, PTS, pterostilbene, PKA, protein kinase A, RSV, resveratrol, SIRT1, sirtuin 1, SUV, standardised uptake value, TRPV1, transient receptor potential vanilloid 1, UCP1, uncoupling protein 1, WAT, white adipose tissue

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          Abstract

          Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.

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          Most cited references226

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          A simple practice guide for dose conversion between animals and human

          Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
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            Identification and Importance of Brown Adipose Tissue in Adult Humans

            Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism. 2009 Massachusetts Medical Society
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              Cold-activated brown adipose tissue in healthy men.

              Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry. Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation. The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity. 2009 Massachusetts Medical Society
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                Author and article information

                Conference
                Proc Nutr Soc
                Proc Nutr Soc
                PNS
                The Proceedings of the Nutrition Society
                Cambridge University Press (Cambridge, UK )
                0029-6651
                1475-2719
                August 2020
                15 April 2020
                : 79
                : 3
                : 338-356
                Affiliations
                [1]Institute of Food, Nutrition and Health, ETH Zurich , Schwerzenbach, Switzerland
                Author notes
                [* ] Corresponding author: C. Wolfrum, email christian-wolfrum@ 123456ethz.ch
                Article
                S0029665120006928
                10.1017/S0029665120006928
                7663322
                32290888
                5e2c7dfb-47df-47bc-b0f4-a488a0c48a17
                © The Authors 2020

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

                The 13th European Nutrition Conference (FENS 2019)
                Convention Centre, Dublin, Ireland
                15–18 October 2019
                History
                Page count
                References: 222, Pages: 19
                Categories
                Fens 2019
                Conference on ‘Malnutrition in an obese world: European perspectives’
                Plenary Session

                Nutrition & Dietetics
                brown adipose tissue,browning,energy expenditure,phytochemicals,weight management

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