Corrigendum to “Impaired brown adipose tissue is differentially modulated in insulin-resistant obese wistar and type 2 diabetic Goto-Kakizaki rats” [Biomed. Pharmacother. 142 (2021) 112019]

Systemic administration of dopamine (DA) receptor agonists leads to falls in body temperature. However, the central thermoregulatory pathways modulated by DA have not been fully elucidated. Here we identified a source and site of action contributing to DA's hypothermic action by inhibition of brown adipose tissue (BAT) thermogenesis. Nanoinjection of the type 2 and type 3 DA receptor (D2R/D3R) agonist, 7-OH-DPAT, in the rostral raphe pallidus area (rRPa) inhibits the sympathetic activation of BAT evoked by cold exposure or by direct activation of NMDA receptors in the rRPa. Blockade of D2R/D3R in the rRPa with nanoinjection of SB-277011A increases BAT thermogenesis, consistent with a tonic release of DA in the rRPa contributing to inhibition of BAT thermogenesis. Accordingly, D2R are expressed in cold-activated and serotonergic neurons in the rRPa and anatomical tracing studies revealed that neurons in the posterior hypothalamus (PH) are a source of dopaminergic input to the rRPa. Disinhibitory activation of PH neurons with nanoinjection of gabazine inhibits BAT thermogenesis, which is reduced by pre-treatment of the rRPa with SB-277011A. In conclusion, the rRPa, the site of sympathetic premotor neurons for BAT, receives a tonically-active, dopaminergic input from the PH that suppresses BAT thermogenesis.

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Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

Hormone and Metabolic Research ◽

10.1055/a-0919-3879 ◽

2019 ◽

Vol 51 (10) ◽

pp. 671-677 ◽

Cited By ~ 7

Author(s):

Maurício Martins da Silva ◽

Carlos Frederico Lima Gonçalves ◽

Leandro Miranda-Alves ◽

Rodrigo Soares Fortunato ◽

Denise P. Carvalho ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Bisphenol A ◽

Brown Adipose Tissue ◽

Tissue Type ◽

Deiodinase Activity ◽

Brown Adipose

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

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Anatomical Locations of Human Brown Adipose Tissue: Functional Relevance and Implications in Obesity and Type 2 Diabetes

Diabetes ◽

10.2337/db12-1430 ◽

2013 ◽

Vol 62 (6) ◽

pp. 1783-1790 ◽

Cited By ~ 138

Author(s):

H. Sacks ◽

M. E. Symonds

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Functional Relevance

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Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats

Antioxidants ◽

10.3390/antiox10091482 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1482

Author(s):

Ahmad Agil ◽

Miguel Navarro-Alarcon ◽

Fatma Abo Zakaib Ali ◽

Ashraf Albrakati ◽

Diego Salagre ◽

...

Keyword(s):

Type 2 Diabetes ◽

Superoxide Dismutase ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Fat ◽

Superoxide Dismutase Activity ◽

Atp Production ◽

Brown Adipose ◽

Zdf Rats

Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted.

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Thermogenic genes are blunted whereas brown adipose tissue identity is preserved in human obesity

10.1101/2020.05.07.082057 ◽

2020 ◽

Cited By ~ 1

Author(s):

Naja Z. Jespersen ◽

Maja W. Andersen ◽

Verena H. Jensen ◽

Thit W Stærkær ◽

Mai C.K. Severinsen ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Selective Reduction ◽

Tracer Uptake ◽

Normal Weight ◽

Molecular Characteristics ◽

Human Obesity ◽

Brown Adipose ◽

Thermogenic Adipocytes

AbstractObesity associates with a reduction in cold-induced glucose tracer uptake in brown adipose tissue in humans, suggesting loss of thermogenic capacity. We therefore hypothesized that a whitening of BAT occurs in obesity and assessed the molecular characteristics of deep neck BAT in a cohort of 24 normal weight, 24 overweight and 22 obese individuals in comparison with subcutaneous abdominal white adipose tissue (WAT). We found that the major marker of BAT thermogenesis, UCP1, was associated with central but not general obesity. We performed transcriptomic analysis of BAT in a cohort of 27 individuals classified as normal weight, over-weight or obese, and additionally four subjects with type 2 diabetes (T2DM), dispersed among the 3 BMI groups. We identified 3204 differentially expressed genes between BAT and WAT in samples from normal weight individuals, including genes involved in thermogenesis, but also revealing differences in developmental and immune system related genes. In BAT from individuals with overweight or obesity, 202 genes were downregulated and 66 of these were involved in cellular respiratory pathways, likely reflecting previously observed reduction in thermogenic function with obesity. Importantly, most BAT selective genes were not affected, and isolated adipose progenitors differentiated into thermogenic adipocytes with equal frequency regardless of BMI group. In conclusion, our data suggest a retained BAT identity, with a selective reduction of thermogenic genes, in human obesity.

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The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue

Journal of Clinical Investigation ◽

10.1172/jci200113803 ◽

2001 ◽

Vol 108 (9) ◽

pp. 1379-1385 ◽

Cited By ~ 307

Author(s):

Lucia A. de Jesus ◽

Suzy D. Carvalho ◽

Mirian O. Ribeiro ◽

Mark Schneider ◽

Sung-Woo Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Iodothyronine Deiodinase ◽

Adaptive Thermogenesis ◽

Brown Adipose

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Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in mice

Biochemical Journal ◽

10.1042/bcj20170736 ◽

2018 ◽

Vol 475 (3) ◽

pp. 561-569 ◽

Cited By ~ 11

Author(s):

Blake W. Dallon ◽

Brian A. Parker ◽

Aimee E. Hodson ◽

Trevor S. Tippetts ◽

Mitchell E. Harrison ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Mitochondrial Respiration ◽

Insulin Treatment ◽

Uncoupling Protein ◽

Mitochondrial Uncoupling ◽

Adipose Tissue Depots ◽

Brown Adipose ◽

A Site

The purpose of the present study was to determine the effects of prolonged hyperinsulinemia on mitochondrial respiration and uncoupling in distinct adipose tissue depots. Sixteen-week-old male mice were injected daily with placebo or insulin to induce an artificial hyperinsulinemia for 28 days. Following the treatment period, mitochondrial respiration and degree of uncoupling were determined in permeabilized perirenal, inguinal, and interscapular adipose tissue. White adipose tissue (WAT) mitochondria (inguinal and perirenal) respire at substantially lower rates compared with brown adipose tissue (BAT). Insulin treatment resulted in a significant reduction in mitochondrial respiration in inguinal WAT (iWAT) and interscapular BAT (iBAT), but not in perirenal WAT (pWAT). Furthermore, these changes were accompanied by an insulin-induced reduction in UCP-1 (uncoupling protein 1) and PGC-1α in iWAT and iBAT only, but not in pWAT or skeletal muscle. Compared with adipose tissue mitochondria in placebo conditions, adipose tissue from hyperinsulinemic mice manifested a site-specific reduction in mitochondrial respiration probably as a result of reduced uncoupling. These results may help explain weight gain so commonly seen with insulin treatment in type 2 diabetes mellitus.

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Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2014-0014 ◽

2014 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Jennifer Honek ◽

Sharon Lim ◽

Carina Fischer ◽

Hideki Iwamoto ◽

Takahiro Seki ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Causes Of Death ◽

Brown Adipose ◽

Common Causes ◽

Brown Adipose Tissue Thermogenesis ◽

Thermogenic Capacity

AbstractThe number of obese and overweight individuals is globally rising, and obesity-associated disorders such as type 2 diabetes, cardiovascular disease and certain types of cancer are among the most common causes of death. While white adipose tissue is the key player in the storage of energy, active brown adipose tissue expends energy due to its thermogenic capacity. Expanding and activating brown adipose tissue using pharmacological approaches therefore might offer an attractive possibility for therapeutic intervention to counteract obesity and its consequences for metabolic health.

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