scholarly journals Effects of Electroacupuncture on PGC-1αExpression in Brown Adipose Tissue

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hongyin Du ◽  
Cuisong Zhou ◽  
Hui Wu ◽  
Tianyue Shan ◽  
Zhenjue Wu ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Molecular Mechanism ◽  
Mitochondrial Protein ◽  
Control Group ◽  
Adipose Tissues ◽  
Increase Energy Expenditure ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
Electroacupuncture Treatment

The inducible coactivator PGC-1αplays master regulator in mitochondrial biogenesis and thermogenesis in brown adipose tissues (BATs). BAT is a natural antiobesity organ which dissipates chemical energy in the form of heat through specialized mitochondrial protein UCP-1. Eletroacupuncture (EA) has been widely used as an alternative treatment for obesity and its related disorders such as type 2 diabetes. The molecular mechanism of electroacupuncture on treatment of obesity is still unclear. We hypothesized that electroacupuncture induced PGC-1αexpression to increase the energy expenditure in BAT. Rats were randomly divided into control group and electroacupuncture treatment group. We investigated the effects of electroacupuncture at Zusanli (ST36) acupoint on the expressions of PGC-1αand its associated genes in the BAT of rats using real-time PCR and western blotting. We found that electroacupuncture effectively induces the expression of PGC-1αand UCP-1 by 4-fold and 5-fold in the BAT of rats, respectively. Our results indicated that the molecular mechanism of electroacupuncture for the treatment of obesity may be, or at least partially, through induction of both PGC-1αand UCP-1 expressions to increase energy expenditure in BAT.

scholarly journals Nanotechnology advances towards development of targeted-treatment for obesity

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicole Remaliah Samantha Sibuyi ◽  
Koena Leah Moabelo ◽  
Mervin Meyer ◽  
Martin Opiyo Onani ◽  
Admire Dube ◽  
...  
Keyword(s):  
Lifestyle Modification ◽  
Mortality Rates ◽  
Proof Of Concept ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Inhibition Of Angiogenesis ◽  
Healthy Body Weight ◽  
Treatment Of Obesity ◽  
Obesity Drugs

AbstractObesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modification or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specificity and unsustainable weight loss effects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side effects, and enhanced efficacy. These effects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbidities.

scholarly journals Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

2021 ◽  
Author(s):  
Rajan Singh ◽  
Albert Barrios ◽  
Golnaz Dirakvand ◽  
Shehla Pervin
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Body Fat ◽  
Metabolic Diseases ◽  
Metabolic Health ◽  
Increase Energy Expenditure ◽  
Brown Adipose ◽  
Adult Humans ◽  
Treatment Of Obesity

Obesity-associated metabolic abnormalities comprise of a cluster of conditions including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. Variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. Substantially decreased BAT activity in individuals with obesity indicates a role for BAT in setting of human obesity. On the other hand, BAT mass and its prevalence has been reported to correlate with lower body mass index (BMI), decreased age and glucose levels, leading to lower incidence of cardio metabolic diseases. Increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. Deeper understanding of the role of BAT in human metabolic health and its inter-relationship with body fat distribution and deciphering proper strategies to increase energy expenditure by either increasing functional BAT mass, or inducing white adipose browning holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.

scholarly journals Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes

2012 ◽  
Vol 2 (S2) ◽  
pp. S37-S42 ◽  
Author(s):  
T Grenier-Larouche ◽  
S M Labbé ◽  
C Noll ◽  
D Richard ◽  
A C Carpentier
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Metabolic Inflexibility

scholarly journals Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 308 ◽  
Author(s):  
Hyo-Geun Lee ◽  
Yu An Lu ◽  
Xining Li ◽  
Ji-Min Hyun ◽  
Hyun-Soo Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Red Seaweed ◽  
High Fat ◽  
Adipose Tissues ◽  
Ppar Γ ◽  
Brown Adipose ◽  
Treatment Of Obesity

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

scholarly journals Protein kinase A induces UCP1 expression in specific adipose depots to increase energy expenditure and improve metabolic health

2016 ◽  
Vol 311 (1) ◽  
pp. R79-R88 ◽  
Author(s):  
Lorna M. Dickson ◽  
Shriya Gandhi ◽  
Brian T. Layden ◽  
Ronald N. Cohen ◽  
Barton Wicksteed
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Cell Function ◽  
Uncoupling Protein ◽  
Metabolic Health ◽  
Regulatory Subunit ◽  
Increase Energy Expenditure ◽  
Brown Adipose ◽  
Β Cell Function ◽  
Pka Regulatory Subunit

Adipose tissue PKA has roles in adipogenesis, lipolysis, and mitochondrial function. PKA transduces the cAMP signal downstream of G protein-coupled receptors, which are being explored for therapeutic manipulation to reduce obesity and improve metabolic health. This study aimed to determine the overall physiological consequences of PKA activation in adipose tissue. Mice expressing an activated PKA catalytic subunit in adipose tissue (Adipoq-caPKA mice) showed increased PKA activity in subcutaneous, epididymal, and mesenteric white adipose tissue (WAT) depots and brown adipose tissue (BAT) compared with controls. Adipoq-caPKA mice weaned onto a high-fat diet (HFD) or switched to the HFD at 26 wk of age were protected from diet-induced weight gain. Metabolic health was improved, with enhanced insulin sensitivity, glucose tolerance, and β-cell function. Adipose tissue health was improved, with smaller adipocyte size and reduced macrophage engulfment of adipocytes. Using metabolic cages, we found that Adipoq-caPKA mice were shown to have increased energy expenditure, but no difference to littermate controls in physical activity or food consumption. Immunoblotting of adipose tissue showed increased expression of uncoupling protein-1 (UCP1) in BAT and dramatic UCP1 induction in subcutaneous WAT, but no induction in the visceral depots. Feeding a HFD increased PKA activity in epididymal WAT of wild-type mice compared with chow, but did not change PKA activity in subcutaneous WAT or BAT. This was associated with changes in PKA regulatory subunit expression. This study shows that adipose tissue PKA activity is sufficient to increase energy expenditure and indicates that PKA is a beneficial target in metabolic health.

Glucagon stimulation of brown adipose tissue growth and thermogenesis

1987 ◽  
Vol 252 (1) ◽  
pp. R160-R165 ◽  
Author(s):  
C. J. Billington ◽  
T. J. Bartness ◽  
J. Briggs ◽  
A. S. Levine ◽  
J. E. Morley
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Lipoprotein Lipase ◽  
Mitochondrial Protein ◽  
Tissue Growth ◽  
Whole Body ◽  
Control Group ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Despite long-standing observations of a whole-body thermogenic effect of glucagon, the role of glucagon in activating thermogenesis in brown adipose tissue has not often been studied. We investigated the ability of administered glucagon to produce alterations in brown adipose tissue similar to changes produced by accepted stimuli of brown fat activity: cold, norepinephrine, and overfeeding. Eighteen days of glucagon injections (1 mg/kg) to male Sprague-Dawley rats produced, relative to saline-injected controls, decreases in feed efficiency and increases in brown adipose tissue weight, protein content, DNA content, and mitochondrial mass as reflected in cytochrome oxidase activity. The observed changes were similar, though of lesser magnitude, to changes produced in these same parameters induced by administration of norepinephrine (250 micrograms/kg) for a positive control group. Four days of glucagon administration (1 mg/kg) produced increases in specific activity of cytochrome oxidase and lipoprotein lipase. After 8 days of glucagon administration, changes in whole-pad activity similar to those seen with 18 days of administration were present. Glucagon also increased whole-pad lipoprotein lipase activity after 4 and 8 days. Surgically denervated interscapular brown adipose tissue retained its ability to respond to exogenous glucagon, though the magnitude of the response was diminished. Guanosine 5'-diphosphate (GDP) binding to brown adipose tissue mitochondria was measured as an assessment of functional state after 5 days of glucagon (1 mg/kg). There was an increase in GDP binding relative to controls whether expressed as picomoles per milligram mitochondrial protein or nanomoles per pad.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Nutritional System

2021 ◽  
pp. 215-224
Author(s):  
Saverio Cinti
Keyword(s):  
Insulin Resistance ◽  
Fundamental Property ◽  
Whole Body ◽  
Fat Cells ◽  
Adipose Tissues ◽  
Functional Activities ◽  
Brown Adipose ◽  
Influence Functional ◽  
Adipose Organ

AbstractThe white and brown adipose tissues are organized to form a true organ. They have a different anatomy and perform different functions, but they collaborate thanks to their ability to convert mutually and reversibly following physiological stimuli. This implies a new fundamental property for mature cells, which would be able to reversibly reprogram their genome under physiological conditions. The subcutaneous mammary gland provides another example of their plasticity. Here fat cells are reversibly transformed into glands during pregnancy and breastfeeding. The obese adipose organ is inflamed because hypertrophic fat cells, typical of this condition, die and their cellular residues must be reabsorbed by macrophages. The molecules produced by these cells during their reabsorption work interfere with the insulin receptor, and this induces insulin resistance, which ultimately causes type 2 diabetes. The adipose organ collaborates with those of digestion. Both produce hormones that can influence the nutritional behavior of individuals. They produce molecules that mutually influence functional activities including thermogenesis, which contributes to the interruption of the meal. The nutrients are absorbed by the intestine, stored in the adipose organ, and distributed by them to the whole body between meals. Distribution includes offspring during breastfeeding. The system as a whole is therefore called the nutritional system.

scholarly journals Repurposing doxepin to ameliorate steatosis and hyperglycemia by activating FAM3A signaling pathway

2020 ◽  
Author(s):  
Ada Admin ◽  
Zhenzhen Chen ◽  
Xiangyang Liu ◽  
Yanjin Luo ◽  
Junpei Wang ◽  
...  
Keyword(s):  
Mitochondrial Protein ◽  
Drug Repurposing ◽  
Atp Synthesis ◽  
Diabetic Patients ◽  
Lipid Deposition ◽  
Diabetic Mice ◽  
Adipose Tissues ◽  
Atp Production ◽  
Glucose And Lipid Metabolism ◽  
Brown Adipose

Mitochondrial protein FAM3A suppresses hepatic gluconeogenesis and lipogenesis. This study aimed to screen drug(s) that activates FAM3A expression, and evaluate its effect(s) on hyperglycemia and steatosis. Drug-repurposing methodology predicted that antidepressive drug doxepin was among the drugs that potentially activated FAM3A expression. Doxepin was further validated to stimulate the translocation of transcription factor HNF4a from the cytoplasm into the nucleus, where it promoted FAM3A transcription to enhance ATP synthesis, suppress gluconeogenesis and reduce lipid deposition in hepatocytes. HNF4a antagonism or FAM3A deficiency blunted doxepin-induced suppression on gluconeogenesis and lipid deposition in hepatocytes. Doxepin administration attenuated hyperglycemia, steatosis and obesity in obese diabetic mice with upregulated FAM3A expression in liver and brown adipose tissues. Notably, doxepin failed to correct dysregulated glucose and lipid metabolism in FAM3A-deficient mice fed on HFD. Doxepin’s effects on ATP production, Akt activation, gluconeogenesis and lipogenesis repression were also blunted in FAM3A-deficient mouse livers. In conclusion, FAM3A is a therapeutical target for diabetes and steatosis. Antidepressive drug doxepin activates FAM3A signaling pathways in liver and brown adipose tissues to improve hyperglycemia and steatosis of obese diabetic mice. Doxepin might be preferentially recommended as antidepressive drug in potential treatment of diabetic patients complicated with depression.

scholarly journals Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice

2016 ◽  
Vol 310 (8) ◽  
pp. E676-E687 ◽  
Author(s):  
Tomoya Sakamoto ◽  
Takahiro Nitta ◽  
Koji Maruno ◽  
Yu-Sheng Yeh ◽  
Hidetoshi Kuwata ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Whole Body ◽  
Marker Genes ◽  
Adipose Tissues ◽  
Expression Levels ◽  
Beige Adipocytes ◽  
Thermogenic Adipocytes

Emergence of thermogenic adipocytes such as brown and beige adipocytes is critical for whole body energy metabolism. Promoting the emergence of these adipocytes, which increase energy expenditure, could be a viable strategy in treating obesity and its related diseases. However, little is known regarding the mechanisms that regulate the emergence of these adipocytes in obese adipose tissue. Here, we demonstrated that classically activated macrophages (M1 Mϕ) suppress the induction of thermogenic adipocytes in obese adipose tissues of mice. Cold exposure significantly induced the expression levels of uncoupling protein-1 (UCP1), which is a mitochondrial protein unique in thermogenic adipocytes, in C57BL/6 mice fed a normal diet. However, UCP1 induction was significantly suppressed in adipose tissues of C57BL/6 mice fed a high-fat diet, into which M1 Mϕ infiltrated. Depletion of M1 Mϕ using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-α (TNFα) in the adipose tissues. Importantly, consistent with the observed changes in the expression levels of marker genes for thermogenic adipocytes, combination treatment of clodronate liposome and cold exposure resulted in metabolic benefits such as lowered body weight and blood glucose level in obese mice. Moreover, intraperitoneal injection of recombinant TNFα protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 Mϕ suppress the induction of thermogenic adipocytes in obese adipose tissues via TNFα. This report suggests that inflammation induced by infiltrated Mϕ could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues.

Modulation of energy balance by fibroblast growth factor 21

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Carlos A. Aguilar-Salinas
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Metabolic Syndrome ◽  
Brown Adipose

AbstractFibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through “browning” of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.

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