Understanding the Biology of Thermogenic Fat: Is Browning A New Approach to the Treatment of Obesity?

Vargas‐Castillo, Ariana; Fuentes-Romero, Rebeca; Rodríguez-López, Leonardo Alejandro; Torres, Nimbe; Tovar, Armando R.

doi:10.1016/j.arcmed.2017.10.002

Cited by 87 publications

(88 citation statements)

References 128 publications

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“…Monitoring resistance to thyroid hormone could be used to evaluate the intended reversal of the abnormal energy balance. Interestingly, where traditional interventions of food intake reduction and physical exercise increase seem to fail, new treatments trying to modify the activity of uncoupling proteins have been proposed (2,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence suggests that hyperthyroxinemia may be cross-sectionally and prospectively associated with type 2 diabetes (1). This is at odds with the physiological metabolism-activating action of thyroid hormones, which is considered capable of ameliorating obesity-related morbidities (2). It is also in conflict with the increased incidence of diabetes reported among patients with hypothyroidism (3) and with the increased prevalence of metabolic syndrome described in the upper-normal range of the pituitary thyroid-stimulating hormone (TSH) (also known as thyrotropin) (4), a range associated with lower thyroid activity.…”

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confidence: 99%

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Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

et al. 2018

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OBJECTIVEDiabetes prevalence and incidence increase among individuals with hypothyroidism but also among those with hyperthyroxinemia, which seems contradictory. Both high free thyroxine (fT4) and high thyroid-stimulating hormone (TSH) are present in the resistance to thyroid hormone syndrome. A mild acquired resistance to thyroid hormone might occur in the general population and be associated with diabetes. We aimed to analyze the association of resistance to thyroid hormone indices (the Thyroid Feedback Quantile-based Index [TFQI], proposed in this work, and the previously used Thyrotroph T4 Resistance Index and TSH Index) with diabetes. RESEARCH DESIGN AND METHODSWe calculated the aforementioned resistance to thyroid hormone indices based on a U.S. representative sample of 5,129 individuals ‡20 years of age participating in the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Also, to approximate TFQI, a U.S.-referenced Parametric TFQI (PTFQI) can be calculated with the spreadsheet formula 5NORM.DIST(fT4_cell_in_pmol_per_L,10.075, 2.155,TRUE)1NORM.DIST(LN(TSH_cell_in_mIU_per_L),0.4654,0.7744,TRUE)21. Outcomes of interest were glycohemoglobin ‡6.5%, diabetes medication, diabetes-related deaths (diabetes as contributing cause of death), and additionally, in a fasting subsample, diabetes and metabolic syndrome. Logistic and Poisson regressions were adjusted for sex, age, and race/ethnicity. RESULTSOdd ratios for the fourth versus the first quartile of TFQI were 1.73 (95% CI 1.32, 2.27) (P trend 5 0.002) for positive glycohemoglobin and 1.66 (95% CI 1.31, 2.10) (P trend 5 0.001) for medication. Diabetes-related death rate ratio for TFQI being above versus below the median was 4.81 (95% CI 1.01, 22.94) (P trend 5 0.015). Further adjustment for BMI and restriction to normothyroid individuals yielded similar results. Per 1 SD in TFQI, odds increased 1.13 (95% CI 1.02, 1.25) for diabetes and 1.16 (95% CI 1.02, 1.31) for metabolic syndrome. The other resistance to thyroid hormone indices showed similar associations for diabetes-related deaths and metabolic syndrome. CONCLUSIONSHigher values in resistance to thyroid hormone indices are associated with obesity, metabolic syndrome, diabetes, and diabetes-related mortality. Resistance to thyroid hormone may reflect energy balance problems driving type 2 diabetes. These indices may facilitate monitoring treatments focused on energy balance.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

et al. 2018

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“…Since obesity is involved in the increased onset of many diseases, much attention has been focused on targeting food components that may help prevent obesity. For obesity prevention by food components, the following strategies appear promising: inhibition of adipocyte differentiation (5), modulation of lipid metabolism (inhibition of lipogenesis and promotion of lipolysis) (26), and promotion of energy expenditure, including the formation of beige adipocytes (27). Various food materials and food-derived phytochemicals have been reported to inhibit adipocyte differentiation (23,24,28,29).…”

Section: Discussionmentioning

confidence: 99%

Methylxanthine Derivative-Rich Cacao Extract Suppresses Differentiation of Adipocytes through Downregulation of PPARγ and C/EBPs

Yamashita

Mitani

Wang

et al. 2018

Journal of Nutritional Science and Vitaminology

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Cacao extract (CE) consumption has beneficial effects on human health, such as lowering the risk of obesity. However, the underlying molecular mechanism for the anti-obesity effect of CE remains incompletely understood. Here, we used a 50% aqueous alcohol extract of cacao mass, which is rich in methylxanthine derivatives (about 11%) and poor in flavan-3-ols (less than 1%), and assessed the suppression effects of this extract on adipocyte differentiation to investigate the anti-obesity mechanism. CE dose-dependently decreased fat accumulation in 3T3-L1 cells without affecting cell viability. CE also dose-dependently decreased the protein and gene expression levels of two adipogenesis-related transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). Moreover, CE decreased protein expression levels of sterol regulatory element-binding protein 1 (SREBP1) and its downstream fatty acid synthase (FAS), which was accompanied by the retained localization of SREBP1 in the cytoplasm of 3T3-L1 cells. After ICR mice were fed a diet containing 1% CE for 1 wk, their white adipose tissue weight was lower, whereas their brown adipose tissue weight was higher compared with those of control animals. Additionally, the protein expression levels of PPARγ, C/EBPs, SREBP1, and FAS in the white adipose tissue of these mice were also lower than those in control animals. In contrast, diet supplementation with CE induced higher levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream acetyl-CoA carboxylase. In conclusion, methylxanthine derivative-rich CE decreases fat accumulation in adipocytes by downregulating the expression of the adipocyte differentiation master regulators through the activation of AMPK.

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“…Pharmacological treatment and dietary strategies aimed at promoting the transition from white to beige fat cells have been considered to fight obesity. β3-adrenergic agonists and dietary-derived molecules such as resveratrol (red wine) and capsaicin (spicy pepper) are able to activate the expression of thermogenic genes in white adipocytes, resulting in the thermal conversion of lipids and their conversion into brown/beige cells [126].…”

Section: Mirna: a Factor In Multifactorial Diseasesmentioning

confidence: 99%

miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

Conti

Varano

Simioni

et al. 2020

Cells

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microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

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Understanding the Biology of Thermogenic Fat: Is Browning A New Approach to the Treatment of Obesity?

Cited by 87 publications

References 128 publications

Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

Methylxanthine Derivative-Rich Cacao Extract Suppresses Differentiation of Adipocytes through Downregulation of PPARγ and C/EBPs

miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

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