Brown adipose tissue: what have we learned since its recent identification in human adults

Halpern, Bruno; Mancini, Márcio C.; Halpern, Alfredo

doi:10.1590/0004-2730000003492

Cited by 21 publications

(28 citation statements)

References 99 publications

(166 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite the very small sample size, the increase was observed in all patients, suggesting that melatonin may be a potential BAT recruiter that should be taken into consideration in further studies in humans, at least in situations in which a reduction in melatonin production occurs. Many experimental studies associated melatonin treatment with an increase in BAT mass as well as melatonin deficiency with a decrease in BAT mass, but these data were restricted to animal studies, mainly hibernating animals (3), and were obtained before the identification of active BAT in human adults (6)(7)(8). Today, BAT is being studied in view of its possible relation with obesity, type 2 diabetes, and other metabolic diseases, and potential BAT activators and recruiters have been proposed (20) as adjuvant treatment of these diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) showed that human adults present active BAT, especially after cold exposure (6,7). This finding quickly led to an exponential increase in BAT research, since activation of BAT leads to increased energy expenditure that could, at least theoretically, be a possible tool for the treatment of obesity and type 2 diabetes (8). Many compounds, including melatonin, have been studied to determine their ability of BAT recruitment and activation, although none of these studies have been carried out in humans (3,9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study

et al. 2019

Self Cite

View full text Add to dashboard Cite

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of b-blocker drugs.Melatonin, a pineal hormone synthesized and released at night that plays a critical role in the synchronization of circadian and seasonal rhythms, has been studied as a key regulator of energy metabolism in many animal species for a long time (1,2). Pinealectomized rats show increased body weight gain and metabolic disturbances that are prevented by daily melatonin supplementation at night, without decreasing energy intake (1-5). This suggests that melatonin also regulates energy metabolism by its action on energy expenditure, possibly as related to the activation of brown adipose tissue (

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The effect of decreased lipid accumulation in canine adipocytes by encapsulated KO xenograft can have important implications for treatment of metabolic diseases, particularly obesity. Dogs and humans have high natal levels of thermogenic brown fat, which is gradually decreased in adulthood rendering them susceptible to obesity and insulin resistance . Obesity is considered to be a modern epidemic influencing 30% of world population .…”

Section: Discussionmentioning

confidence: 99%

Aldehyde dehydrogenase 1 a1 regulates energy metabolism in adipocytes from different species

Yang

Adin

Shen

et al. 2017

Xenotransplantation

View full text Add to dashboard Cite

Background Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for inter-species crosstalk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes. Deficient retinoic acid production in aldehyde dehydrogenase 1 family fember A1 (Aldh1a1) knock out adipocytes (KO) inhibits adipogenesis and increase thermogenesis. Here we test the role Aldh1a1 in regulation of lipid metabolism in xenocultures. Methods Murine wide type (WT) and KO preadipocytes were encapsulated into a poly-L-lysine polymer that allows exchange of humoral factors <32kD via nanopores. Encapsulated murine adipocytes were co-incubated with primary differentiated canine adipocytes. Then, expression of adipogenic and thermogenic genes in differentiated canine adipocytes were detected by real-time polymerase chain reaction (PCR). The regulatory factors in WT and KO cells were identified by comparison of secretome using proteomics and in transcriptome by gene microarray. Results Co-culture of encapsulated mouse KO vs. WT adipocytes increased expression of peroxisome proliferator-activated receptor gamma (Pparg), but reduced expression of its target genes fatty acid binding protein 4 (Fabp4), and adipose triglyceride lipase (Atgl) in canine adipocytes, suggesting inhibition of PPARγ activation. Co-culture with KO adipocytes also induced expression of Ucp1 in canine adipocytes compared to expression with WT adipocytes. Cumulatively, murine KO compared to WT adipocytes decreased lipid accumulation in canine adipocytes. Comparative proteomics revealed significantly higher levels of vitamin A carriers, retinol binding protein 4 (RBP4) and lipokalin 2 (LCN2) in KO vs WT adipocytes. Conclusion Our data demonstrate the functional exchange of regulatory factors between adipocytes from different species for regulation of energy balance. RBP4 and LCN2 appear to be involved in the transport of retinoids for regulation of lipid accumulation and thermogenesis in xenocultures. While the rarity of thermogenic adipocytes in humans and dogs precludes their use for autologous transplantation, our study demonstrates that xenotransplantation of engineered cells could be a potential solution for reduction of obesity in dogs and a strategy for translation to patients.

show abstract

“…These reviews have summarized the various approaches of imaging BAT and their shortcomings [11]. Other reviews have pointed to the value of diet-induced thermogenesis [12]. More recently, pharmacological strategies for BAT recruitment have been reported as a target of obesity and insulin sensitivity [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity

Baranwal¹,

Schade²

2016

CDR

View full text Add to dashboard Cite

Objective: Increasing efforts are being made towards pharmacologic activation of brown adipose tissue (BAT) in animals and humans for potential use in the treatment of obesity and diabetes. We and others have reported a number of animal studies using either experimental or therapeutic drugs. There are now efforts to translate these findings to human studies. The goal of this review is to evaluate the various drugs currently being used that have the potential for BAT activation.Methods: Drugs were classified into 4 classes based on their mechanism of action. Class 1 drugs include the use of β3 adrenoceptor agonists for BAT activation. Class 2 drugs include drugs that affect norepinephrine levels and activate BAT with the potential of reducing obesity. Class 3 includes activators of peroxisome proliferator-activated receptor-γ in pursuit of lowering blood sugar, weight loss and diabetes and finally Class 4 includes natural products and other emerging drugs with limited information on BAT activation and their effects on diabetes and weight loss.Results: Class 1 drugs are high BAT activators followed by Class 2 and 3. Some of these drugs have now been extended to diabetes and obesity animal models and human BAT studies. Drugs in Class 3 are used clinically for Type 2 diabetes, but the extent of BAT involvement is unclear.Conclusion: Further studies on the efficacy of these drugs in diabetes and measuring their effects on BAT activation using noninvasive imaging will help in establishing a clinical role of BAT.

show abstract

Brown adipose tissue: what have we learned since its recent identification in human adults

Cited by 21 publications

References 99 publications

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study

Aldehyde dehydrogenase 1 a1 regulates energy metabolism in adipocytes from different species

Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity

Contact Info

Product

Resources

About