Metabolic syndrome, variously known also as syndrome X, insulin resistance, etc., is defined by WHO as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Though there is some variation in the definition by other health care organization, the differences are minor. With the successful conquest of communicable infectious diseases in most of the world, this new non-communicable disease (NCD) has become the major health hazard of modern world. Though it started in the Western world, with the spread of the Western lifestyle across the globe, it has become now a truly global problem. The prevalence of the metabolic syndrome is often more in the urban population of some developing countries than in its Western counterparts. The two basic forces spreading this malady are the increase in consumption of high calorie-low fiber fast food and the decrease in physical activity due to mechanized transportations and sedentary form of leisure time activities. The syndrome feeds into the spread of the diseases like type 2 diabetes, coronary diseases, stroke, and other disabilities. The total cost of the malady including the cost of health care and loss of potential economic activity is in trillions. The present trend is not sustainable unless a magic cure is found (unlikely) or concerted global/governmental/societal efforts are made to change the lifestyle that is promoting it. There are certainly some elements in the causation of the metabolic syndrome that cannot be changed but many are amenable for corrections and curtailments. For example, better urban planning to encourage active lifestyle, subsidizing consumption of whole grains and possible taxing high calorie snacks, restricting media advertisement of unhealthy food, etc. Revitalizing old fashion healthier lifestyle, promoting old-fashioned foods using healthy herbs rather than oil and sugar, and educating people about choosing healthy/wholesome food over junks are among the steps that can be considered.

/pdf/the-global-epidemic-of-the-metabolic-syndrome-qvn7llo3ls.pdf

The Global Epidemic of the Metabolic Syndrome.

https://www.cell.com/cell/pdf/S0092-8674(13)01546-8.pdf

What We Talk About When We Talk About Fat

Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

/pdf/biochemistry-of-adipose-tissue-an-endocrine-organ-j03l3zj770.pdf

Biochemistry of adipose tissue: an endocrine organ

Accumulation of excess white adipose tissue (WAT) has deleterious consequences for metabolic health. The activation of brown adipose tissue (BAT), the primary organ for heat production, confers beneficial effects on adiposity, insulin resistance and hyperlipidaemia, at least in mice. As the amount of metabolically active BAT seems to be particularly low in patients with obesity or diabetes mellitus who require immediate therapy, new avenues are needed to increase the capacity for adaptive thermogenesis. In this light, we review the findings that BAT in human adults might consist of not only classic brown adipocytes but also inducible brown adipocytes (also called beige, brown-in-white, or brite adipocytes), which are phenotypically distinct from both white and brown adipocytes. Stimulating the development of beige adipocytes in WAT (so called 'browning') might reduce adverse effects of WAT and could help to improve metabolic health. This article focuses on the development and regulatory control of beige adipocytes at the transcriptional and hormonal levels. Emerging insights into the metabolic role of beige adipocytes are also discussed, along with the developments that can be expected from these promising targets for therapy of metabolic disease in the future.

Adipose tissue browning and metabolic health

https://www.cell.com/cell-metabolism/pdf/S1550-4131%2814%2900560-9.pdf

Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist

Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/67000/67803/JCI67803.v2.pdf

Recruited brown adipose tissue as an antiobesity agent in humans

Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20–73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 °C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/oby.2011.125

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans.

Brown adipose tissue (BAT) can be identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20–28 years underwent FDG-PET after 2-h cold exposure at 19 °C with light-clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining seven showed no detectable uptake (BAT-negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 °C, the energy expenditure of the BAT-positive group estimated by indirect calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the BAT-negative group (1,434 ± 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 ± 293 (P < 0.05) and slightly by 42 ± 114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A positive correlation (P < 0.05) was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 °C in the BAT-positive group, whereas it dropped more markedly (P < 0.01) by 0.60 °C in the BAT-negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold-induced increases in whole-body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/oby.2010.105

Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men.

Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. Some clinical studies have reported an association between BAT and blood glucose in humans. To examine the impact of BAT on glucose metabolism, independent of that of body fatness, age and sex in healthy adult humans. Two hundred and sixty healthy volunteers (184 males and 76 females, 20–72 years old) underwent fluorodeoxyglucose-positron emission tomography and computed tomography after 2 h of cold exposure to assess maximal BAT activity. Blood parameters including glucose, HbA1c and low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol were measured by conventional methods, and body fatness was estimated from body mass index (BMI), body fat mass and abdominal fat area. The impact of BAT on body fatness and blood parameters was determined by logistic regression with the use of univariate and multivariate models. Cold-activated BAT was detected in 125 (48%) out of 260 subjects. When compared with subjects without detectable BAT, those with detectable BAT were younger and showed lower adiposity-related parameters such as the BMI, body fat mass and abdominal fat area. Although blood parameters were within the normal range in the two subject groups, HbA1c, total cholesterol and LDL-cholesterol were significantly lower in the BAT-positive group. Blood glucose also tended to be lower in the BAT-positive group. Logistic regression demonstrated that BAT, in addition to age and sex, was independently associated with BMI, body fat mass, and abdominal visceral and subcutaneous fat areas. For blood parameters, multivariate analysis after adjustment for age, sex and body fatness revealed that BAT was a significantly independent determinant of glucose and HbA1c. BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans.

Sayuri Aita

Papers

Recruited brown adipose tissue as an antiobesity agent in humans

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans.

Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men.

Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans.

Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans