scholarly journals MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1056 ◽  
Author(s):  
Indira G.C. Vonhögen ◽  
Hamid el Azzouzi ◽  
Servé Olieslagers ◽  
Aliaksei Vasilevich ◽  
Jan de Boer ◽  
...  

The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3′UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes.

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongcai Ye ◽  
Chunlong Yan ◽  
Huiqiao Zhou ◽  
Yuanyuan Huang ◽  
Meng Dong ◽  
...  

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.


2019 ◽  
Vol 181 (5) ◽  
pp. 473-480 ◽  
Author(s):  
Oliveira Flávia R ◽  
Marcelo Mamede ◽  
Mariana F Bizzi ◽  
Rocha Ana Luiza L ◽  
Cláudia N Ferreira ◽  
...  

Objective To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9–15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7–18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman’s r = −0.630, P = 0.000) and waist circumference (r = −0.592, P = 0.000) but not with plasma irisin levels. Conclusions BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.


2014 ◽  
Vol 170 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Zhaoyun Zhang ◽  
Aaron M Cypess ◽  
Qing Miao ◽  
Hongying Ye ◽  
Chong Wee Liew ◽  
...  

ObjectivePrevious studies have shown that active brown adipose tissue (BAT) is present in adults and may play important roles in the regulation of energy homeostasis. However, nearly every study has been carried out in patients undergoing scanning for cancer surveillance (CS), whose metabolism and BAT activity may not reflect those of healthy individuals. The objective of this study was to investigate the prevalence and predictors of active BAT in Chinese adults, particularly in healthy individuals.DesignA total of 31 088 consecutive subjects aged ≥18 years who had undergone positron emission tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this study.MethodsWe measured BAT activity via18F-fluorodeoxyglucose PET/CT in subjects who had undergone scanning for either a routine medical checkup (MC) or CS in Shanghai. Then, we investigated the predictors of active BAT, particularly in healthy individuals.ResultsIn both groups, the prevalence of BAT was higher in women than in men. Using a multivariate logistic analysis, we found age, sex, BMI, and high thyroid glucose uptake to be significant predictors of BAT activity in the MC group. Similarly, we found age, sex, and BMI to be significant predictors of BAT activity, but not thyroid high glucose uptake, in the CS group.ConclusionsIn Chinese adults, BAT activity inversely correlates with BMI and thyroid high glucose uptake, which reinforces the central role of brown fat in adult metabolism and provides clues to a potential means for treating the metabolic syndrome.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2752
Author(s):  
Kelsey A. Heenan ◽  
Andres E. Carrillo ◽  
Jacob L. Fulton ◽  
Edward J. Ryan ◽  
Jason R. Edsall ◽  
...  

Background: Brown adipose tissue (BAT) provides a minor contribution to diet-induced thermogenesis (DIT)—the metabolic response to food consumption. Increased BAT activity is generally considered beneficial for mammalian metabolism and has been associated with favorable health outcomes. The aim of the current systematic review was to explore whether nutritional factors and/or diet affect human BAT activity. Methods: We searched PubMed Central, Embase and Cochrane Library (trials) to conduct this systematic review (PROSPERO protocol: CRD42018082323). Results: We included 24 eligible papers that studied a total of 2785 participants. We found no mean differences in standardized uptake value of BAT following a single meal or after 6 weeks of L-Arginine supplementation. Resting energy expenditure (REE), however, was increased following a single meal and after supplementation of capsinoid and catechin when compared to a control condition (Z = 2.41, p = 0.02; mean difference = 102.47 (95% CI = 19.28–185.67)). Conclusions: Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.


Author(s):  
Rahel Catherina Loeliger ◽  
Claudia Irene Maushart ◽  
Gani Gashi ◽  
Jaël Rut Senn ◽  
Martina Felder ◽  
...  

Objective Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. Methods We assessed DIT, cold induced thermogenesis (CIT) and maximum BAT activity at three separate study visits within two weeks. DIT was measured by indirect calorimetry during an oral glucose tolerance-test. CIT was assessed as the difference in EE after cold exposure of two hours duration as compared to warm conditions. Maximal activity of BAT was assessed by 18F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with Mirabegron. Results 17 healthy men (mean age 23.4 years, mean BMI 23.2 kg/m2) participated in the study. EE increased from 1908 (±181) kcal/24 hours to 2128 (±277) kcal/24 hours (p<0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1911 (±165) kcal/24 hours to 2096 (±167) kcal/24 hours at 60 minutes (p<0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R2=0.43, p=0.004). However, DIT was not associated with BAT activity (R2=0.015, p=0.64). Conclusion DIT after an oral glucose load was not associated with stimulated 18F-FDG uptake into BAT suggesting that DIT is independent from BAT activity in humans.


Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 388
Author(s):  
Angie S. Xiang ◽  
Corey Giles ◽  
Rebecca K.C. Loh ◽  
Melissa F. Formosa ◽  
Nina Eikelis ◽  
...  

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.


Author(s):  
A.P. Stepanchuk

The risk of developing metabolic complications in obesity depends on the topography of excess adipose tissue. Adipose tissue is the main source of energy and also performs an endocrine function secreting substances that affect the sensitivity of tissues to insulin. The article describes the characteristics of histological preparations of adipose tissue samples taken from the omentum of middle-aged human cadavers with no confirmed diseases of the digestive system and of subcutaneous adipose tissue samples from interscapular region in the human dead foetuses. Microscopy of sections of adipose tissue from the omentum and subcutaneous adipose tissue from the interscapular region of the foetus revealed that it consisted of lobes and microvessels. Lobes of adipose tissue of a human large omentum consist of polygonal white adipocytes containing in their cytoplasm a nucleus displaced to the periphery and a fat drop. The subcutaneous adipose tissue taken from the interscapular region of the foetus consists of brown adipocytes with a nucleus located in the centre of the cytoplasm and surrounded by numerous fat droplets. Brown adipocytes when compared with white adipocyted are smaller and rounded in shape. Brown adipose tissue predominates in women than in men. Brown adipose tissue is not active all the time, but only at low ambient temperatures. In women, brown adipocytes are more saturated with mitochondria than in men. Adipose tissue of a human omentum can be a source of graft implant for restoring abdominal organ defects during extensive surgical operations.


2020 ◽  
Author(s):  
Bruno Halpern ◽  
Marcio C Mancini ◽  
Caroline Mendes ◽  
Camila Maria Longo Machado ◽  
Silvana Prando ◽  
...  

Abstract Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasively and. the gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with melatonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression.Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kasiphak Kaikaew ◽  
Aldo Grefhorst ◽  
Jenny A. Visser

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.


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