Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases

2010 ◽  
Vol 9 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Yihai Cao
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Target ◽  
Metabolic Diseases

Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Therapeutic Agents ◽  
Adipose Tissue Inflammation ◽  
Cellular Mechanisms ◽  
Tissue Inflammation ◽  
Cholesterol Levels ◽  
Naturally Occurring ◽  
Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

scholarly journals Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 622
Author(s):  
Pamela A. Nono Nankam ◽  
Télesphore B. Nguelefack ◽  
Julia H. Goedecke ◽  
Matthias Blüher
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
African Ancestry ◽  
Fat Distribution ◽  
African Women ◽  
European Ancestry ◽  
Whole Body ◽  
Redox Equilibrium ◽  
Systemic Oxidative Stress

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

Unusual increase of Scd1 and Elovl6 expression in rat inguinal adipose tissue

2012 ◽  
Vol 7 (2) ◽  
pp. 192-200
Author(s):  
Jacek Turyn ◽  
Adriana Mika ◽  
Piotr Stepnowski ◽  
Julian Swierczynski
Keyword(s):  
Adipose Tissue ◽  
Food Restriction ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Levels ◽  
Gene Expressions ◽  
Tissue Mass ◽  
Expression Of Genes ◽  
Fat Deposits ◽  
Rat Adipose Tissue

AbstractIt is generally accepted that the location of body fat deposits may play an important role in the risk of developing some endocrine and metabolic diseases. We have studied the effect of food restriction and food restriction/refeeding, often practiced by individuals trying to lose body weight, on the expression of genes which are associated with obesity and certain metabolic disorders in inguinal, epididymal, and perirenal rat white adipose tissues. Gene expression was analyzed by real time semi-quantitative polymerase chain reaction and by Western blot. We found that prolonged food restriction caused a significant decrease of body and adipose tissue mass as well as the increase of Scd1 and Elovl6 gene expressions in all main rat adipose tissue deposits. Food restriction/refeeding caused increases of: a) Scd1 and Elovl6 mRNA levels in adipose tissue, b) Scd1 protein level and c) desaturation index in adipose tissue. The increased expression of both genes was unusually high in inguinal adipose tissue. The results suggest that the increase of Scd1 and Elovl6 gene expressions in white adipose tissue by prolonged food restriction and prolonged food restriction/refeeding may contribute to accelerated fat recovery that often occurs in individuals after food restriction/refeeding.

scholarly journals Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women

2017 ◽  
Vol 102 (12) ◽  
pp. 4588-4595 ◽  
Author(s):  
Natalia Hetemäki ◽  
Hanna Savolainen-Peltonen ◽  
Matti J Tikkanen ◽  
Feng Wang ◽  
Hanna Paatela ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Messenger Rna ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcutaneous Fat ◽  
Estrogen Metabolism ◽  
Serum Samples ◽  
Estrogen Exposure

Abstract Context In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

12,13-diHOME as a new therapeutic target for metabolic diseases

Life Sciences ◽  
2021 ◽  
pp. 120229
Author(s):  
Ana Paula Azevêdo Macêdo ◽  
Vitor Rosetto Muñoz ◽  
Dennys Esper Cintra ◽  
José Rodrigo Pauli
Keyword(s):  
Therapeutic Target ◽  
Metabolic Diseases

scholarly journals CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaiyi Zhang ◽  
Cong Tao ◽  
Jianping Xu ◽  
Jinxue Ruan ◽  
Jihan Xia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Visceral Adipose Tissue ◽  
Antigen Processing ◽  
Metabolic Diseases ◽  
Early Stage ◽  
Large Animal ◽  
Transgenic Pigs ◽  
Inflammatory Signaling ◽  
Visceral Adipose

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn, hIAPP and PNPLA3I148M. Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs’ liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.

scholarly journals TM4SF5 Knockout Protects Mice from Diet-Induced Obesity Partly by Regulating Autophagy in Adipose Tissue

2021 ◽  
Author(s):  
Cheoljun Choi ◽  
Yeonho Son ◽  
Jinyoung Kim ◽  
Yoon Keun Cho ◽  
Abhirup Saha ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxidative Metabolism ◽  
Metabolic Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Regulatory Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Mtorc1 Signaling ◽  
Mitochondrial Oxidative Metabolism

Transmembrane 4 L six family member 5 (TM4SF5) functions as a sensor for lysosomal arginine levels and activates the mammalian target of rapamycin complex 1 (mTORC1). While the mTORC1 signaling pathway plays a key role in adipose tissue metabolism, the regulatory function of TM4SF5 in adipocytes remains unclear. This study aimed to establish a TM4SF5 knockout (KO) mouse model and investigated the effects of TM4SF5 KO on mTORC1 signaling-mediated autophagy and mitochondrial metabolism in adipose tissue. TM4SF5 expression was higher in inguinal white adipose tissue (iWAT) than in brown adipose tissue and significantly upregulated by a high-fat diet (HFD). TM4SF5 KO reduced mTORC1 activation and enhanced autophagy and lipolysis in adipocytes. RNA-seq analysis of TM4SF5 KO mouse iWAT showed that the expression of genes involved in peroxisome proliferator-activated receptor alpha signaling pathways and mitochondrial oxidative metabolism was upregulated. Consequently, TM4SF5 KO reduced adiposity and increased energy expenditure and mitochondrial oxidative metabolism. TM4SF5 KO prevented HFD-induced glucose intolerance and inflammation in adipose tissue. Collectively, our study demonstrated that TM4SF5 regulates autophagy and lipid catabolism in adipose tissue and suggested that TM4SF5 could be therapeutically targeted for the treatment of obesity-related metabolic diseases.

scholarly journals Adipose tissue: from amorphous filler to metabolic mastermind

2021 ◽  
Author(s):  
Silvia Corvera
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Appetite Control ◽  
Fat Storage ◽  
Fuel Distribution ◽  
Adipose Tissue Depots ◽  
Increased Risk ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Hyperplasia

Adipose tissue plays a central role in the control of systemic glucose homeostasis through two major mechanisms: fat storage and secretion of specific cytokines known as adipokines. Fat storage in adipose tissue is critically important, as it prevents lipid deposition in liver and muscle, which in turn results in insulin resistance and increased risk of type 2 diabetes. Secretion of adipokines, such as leptin, protects from fuel depletion through appetite control, and other adipokines control fuel distribution and utilization. Fat storage capacity of adipose tissue increases through two mechanisms, adipocyte hypertrophy and adipocyte hyperplasia. Adipose tissue depots expand differently in diverse individuals and confer varying degrees of metabolic disease risk. There are multiple adipocyte subtypes that together mediate the functions of adipose tissue. They do so through specialized functions such as thermogenesis, which burns fuel to maintain core temperature, and through selective secretion of different adipokines. Much progress has been made in understanding the mechanisms by which adipose tissue controls systemic metabolism, increasing our hope of developing new, effective therapies for metabolic diseases.

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