scholarly journals Brd2 disruption in mice causes severe obesity without Type 2 diabetes

2009 ◽  
Vol 425 (1) ◽  
pp. 71-85 ◽  
Author(s):  
Fangnian Wang ◽  
Hongsheng Liu ◽  
Wanda P. Blanton ◽  
Anna Belkina ◽  
Nathan K. Lebrasseur ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Intolerance ◽  
Severe Obesity ◽  
Healthy Humans ◽  
Brown Adipose ◽  
Metabolically Healthy

Certain human subpopulations are metabolically healthy but obese, or metabolically obese but normal weight; such mutations uncouple obesity from glucose intolerance, revealing pathways implicated in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin. In the present study, we show that wholebody disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue, heat production and expression of mitochondrial uncoupling proteins in brown adipose tissue, reduced macrophage infiltration in white adipose tissue, and lowered blood glucose, leading to an improved metabolic profile and avoiding eventual Type 2 diabetes. Brd2 is highly expressed in pancreatic β-cells, where it normally inhibits β-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, Brd2 normally co-represses PPAR-γ (peroxisome-proliferator-activated receptor-γ) and inhibits adipogenesis. Brd2 knockdown protects 3T3-L1 adipocytes from TNF-α (tumour necrosis factor-α)-induced insulin resistance, thereby decoupling inflammation from insulin resistance. Thus hypomorphic Brd2 shifts energy balance toward storage without causing glucose intolerance and may provide a novel model for obese metabolically healthy humans.

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

Antioxidants ◽  
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.

Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects

2014 ◽  
Vol 19 (1) ◽  
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.

scholarly journals Quantification of adipose tissue insulin sensitivity

2016 ◽  
Vol 64 (5) ◽  
pp. 989-991 ◽  
Author(s):  
Esben Søndergaard ◽  
Michael D Jensen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Resistant ◽  
Healthy Humans ◽  
Metabolic Defects ◽  
Tissue Resistance

In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

More than a simple storage organ: Adipose tissue as a source of adipokines involved in cardiovascular disease

2013 ◽  
Vol 110 (10) ◽  
pp. 641-650 ◽  
Author(s):  
Gersina Rega-Kaun ◽  
Christoph Kaun ◽  
Johann Wojta
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Overweight And Obesity ◽  
Therapeutic Approaches ◽  
Storage Organ ◽  
Pathophysiological Role ◽  
Metabolically Healthy

SummaryOverweight and obesity in many countries have developed into a serious health problem by themselves and by their impact on other pathologies such as insulin resistance, type 2 diabetes, hypertension, heart disease and cancer. The modulation of these diseases by adipose tissue-derived biomolecules, so-called adipokines, could be the key to differentiate between metabolically healthy and unhealthy obesity. This review will discuss the pathophysiological role of selected adipokines, primarily focusing on cardiovascular diseases. Furthermore, we will highlight possible therapeutic approaches, which target these biomolecules.

scholarly journals Cold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity

Biology ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 9 ◽  
Author(s):  
Carmem Peres Valgas da Silva ◽  
Diego Hernández-Saavedra ◽  
Joseph White ◽  
Kristin Stanford
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Lipid Uptake ◽  
Mitochondrial Uncoupling ◽  
Bat Activity ◽  
Brown Adipose

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and exercise training are two stimuli that have been investigated with respect to BAT activation, metabolism, and the contribution of BAT to metabolic health. These two stimuli are of great interest because they have both disparate and converging effects on BAT activation and metabolism. Cold exposure is an effective mechanism to stimulate BAT activity and increase glucose and lipid uptake through mitochondrial uncoupling, resulting in metabolic benefits including elevated energy expenditure and increased insulin sensitivity. Exercise is a therapeutic tool that has marked benefits on systemic metabolism and affects several tissues, including BAT. Compared to cold exposure, studies focused on BAT metabolism and exercise display conflicting results; the majority of studies in rodents and humans demonstrate a reduction in BAT activity and reduced glucose and lipid uptake and storage. In addition to investigations of energy uptake and utilization, recent studies have focused on the effects of cold exposure and exercise on the structural lipids in BAT and secreted factors released from BAT, termed batokines. Cold exposure and exercise induce opposite responses in terms of structural lipids, but an important overlap exists between the effects of cold and exercise on batokines. In this review, we will discuss the similarities and differences of cold exposure and exercise in relation to their effects on BAT activity and metabolism and its relevance for the prevention of obesity and the development of type 2 diabetes.

Liraglutide decreases energy expenditure and does not affect the fat fraction of supraclavicular brown adipose tissue in patients with type 2 diabetes

2020 ◽  
Vol 30 (4) ◽  
pp. 616-624 ◽  
Author(s):  
Huub J. van Eyk ◽  
Elisabeth H.M. Paiman ◽  
Maurice B. Bizino ◽  
Suzanne L. IJzermans ◽  
Fleur Kleiburg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Brown Adipose ◽  
Fat Fraction

scholarly journals Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

Diabetes ◽  
2015 ◽  
Vol 64 (7) ◽  
pp. 2388-2397 ◽  
Author(s):  
Denis P. Blondin ◽  
Sébastien M. Labbé ◽  
Christophe Noll ◽  
Margaret Kunach ◽  
Serge Phoenix ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Oxidative Metabolism ◽  
Brown Adipose ◽  
Selective Impairment
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