scholarly journals Obesity and Infection: Reciprocal Causality

2015 ◽  
pp. S105-S119 ◽  
Author(s):  
V. HAINER ◽  
H. ZAMRAZILOVÁ ◽  
M. KUNEŠOVÁ ◽  
B. BENDLOVÁ ◽  
I. ALDHOON-HAINEROVÁ
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Infectious Agents ◽  
Human Obesity ◽  
Causal Factors ◽  
New Horizons ◽  
Obesity And Diabetes ◽  
Treatment Of Obesity ◽  
Mutual Relations ◽  
Adenovirus 36

Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

scholarly journals Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes

Obesity ◽  
2016 ◽  
Vol 24 (4) ◽  
pp. 820-828 ◽  
Author(s):  
Zuzana Kovacova ◽  
William G. Tharp ◽  
Dianxin Liu ◽  
Wan Wei ◽  
Hui Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Natriuretic Peptide ◽  
Receptor Expression ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Obesity And Diabetes

Cellular and molecular effects of n−3 polyunsaturated fatty acids on adipose tissue biology and metabolism

2008 ◽  
Vol 116 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Pavel Flachs ◽  
Martin Rossmeisl ◽  
Morten Bryhn ◽  
Jan Kopecky
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Tissue Growth ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Active Metabolites ◽  
Metabolic Switch ◽  
Obesity And Diabetes

Adipose tissue and its secreted products, adipokines, have a major role in the development of obesity-associated metabolic derangements including Type 2 diabetes. Conversely, obesity and its metabolic sequelae may be counteracted by modulating metabolism and secretory functions of adipose tissue. LC-PUFAs (long-chain polyunsaturated fatty acids) of the n−3 series, namely DHA (docosahexaenoic acid; C22:6n−3) and EPA (eicosapentaenoic acid; C20:5n−3), exert numerous beneficial effects, such as improvements in lipid metabolism and prevention of obesity and diabetes, which partially result from the metabolic action of n−3 LC-PUFAs in adipose tissue. Recent studies highlight the importance of mitochondria in adipose tissue for the maintenance of systemic insulin sensitivity. For instance, both n−3 LC-PUFAs and the antidiabetic drugs TZDs (thiazolidinediones) induce mitochondrial biogenesis and β-oxidation. The activation of this ‘metabolic switch’ in adipocytes leads to a decrease in adiposity. Both n−3 LC-PUFAs and TZDs ameliorate a low-grade inflammation of adipose tissue associated with obesity and induce changes in the pattern of secreted adipokines, resulting in improved systemic insulin sensitivity. In contrast with TZDs, which act as agonists of PPARγ (peroxisome-proliferator-activated receptor-γ) and promote differentiation of adipocytes and adipose tissue growth, n−3 LC-PUFAs affect fat cells by different mechanisms, including the transcription factors PPARα and PPARδ. Some of the effects of n−3 LC-PUFAs on adipose tissue depend on their active metabolites, especially eicosanoids. Thus treatments affecting adipose tissue by multiple mechanisms, such as combining n−3 LC-PUFAs with either caloric restriction or antidiabetic/anti-obesity drugs, should be explored.

Intricacies of the endothelin system in human obesity: role in the development of complications and potential as a therapeutic target

2020 ◽  
Vol 98 (9) ◽  
pp. 563-569 ◽  
Author(s):  
Francesca Schinzari ◽  
Carmine Cardillo
Keyword(s):  
Adipose Tissue ◽  
Vascular Dysfunction ◽  
Tissue Expansion ◽  
Human Obesity ◽  
Metabolic Complications ◽  
Perivascular Adipose Tissue ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome ◽  
Obesity And Diabetes ◽  
Endothelin System

Activation of the vascular endothelin-1 (ET-1) system is a key abnormality in vascular dysfunction of human obesity, especially in patients developing complications, such as the metabolic syndrome, diabetes, and atherosclerosis. Vascular insulin resistance, an increased insulin-stimulated endothelial production of ET-1 combined with impaired nitric oxide availability, is the hallmark of obesity-related vasculopathy, but dysregulated adipokine release from obese adipose tissue may contribute to the predominance of ET-1-dependent vasoconstriction. ET-1, in turn, might determine unhealthy obese adipose tissue expansion, with visceral and perivascular adipose tissue changes driving the release of inflammatory cytokines and atherogenic chemokines. In addition, ET-1 might also play a role in the development of the metabolic complications of obesity. Studies have shown inhibition of lipoprotein lipase activity by ET-1, with consequent hypertriglyceridemia. Also, ET-1 in pancreatic islets seems to contribute to beta cell dysfunction, hence affecting insulin production and development of diabetes. Moreover, ET-1 may play a role in nonalcoholic steatohepatitis. Recent clinical trials using innovative design have demonstrated that antagonism of ET-type A receptors protects against some complications of obesity and diabetes, such as nephropathy. These findings encourage further investigation to evaluate whether targeting the ET-1 system could afford better protection against other consequences of the obesity epidemic.

Increased GIP signaling induces adipose inflammation via a HIF-1α-dependent pathway and impairs insulin sensitivity in mice

2015 ◽  
Vol 308 (5) ◽  
pp. E414-E425 ◽  
Author(s):  
Shu Chen ◽  
Fumiaki Okahara ◽  
Noriko Osaki ◽  
Akira Shimotoyodome
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Inflammation ◽  
Obesity And Diabetes ◽  
Gut Hormone

Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted in response to dietary fat and glucose. The blood GIP level is elevated in obesity and diabetes. GIP stimulates proinflammatory gene expression and impairs insulin sensitivity in cultured adipocytes. In obesity, hypoxia within adipose tissue can induce inflammation. The aims of this study were 1) to examine the proinflammatory effect of increased GIP signaling in adipose tissues in vivo and 2) to clarify the association between GIP and hypoxic signaling in adipose tissue inflammation. We administered GIP intraperitoneally to misty (lean) and db/db (obese) mice and examined adipose tissue inflammation and insulin sensitivity. We also examined the effects of GIP and hypoxia on expression of the GIP receptor (GIPR) gene and proinflammatory genes in 3T3-L1 adipocytes. GIP administration increased monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration into adipose tissue and increased blood glucose in db/db mice. GIPR and hypoxia-inducible factor-1α (HIF-1α) expressions were positively correlated in the adipose tissue in mice. GIPR expression increased dramatically in differentiated adipocytes. GIP treatment of adipocytes increased MCP-1 and interleukin-6 (IL-6) production. Adipocytes cultured either with RAW 264 macrophages or under hypoxia expressed more GIPR and HIF-1α, and GIP treatment increased gene expression of plasminogen activator inhibitor 1 and IL-6. HIF-1α gene silencing diminished both macrophage- and hypoxia-induced GIPR expression and GIP-induced IL-6 expression in adipocytes. Thus, increased GIP signaling plays a significant role in adipose tissue inflammation and thereby insulin resistance in obese mice, and HIF-1α may contribute to this process.

scholarly journals Thromboxane synthase deficiency improves insulin action and attenuates adipose tissue fibrosis

2015 ◽  
Vol 308 (9) ◽  
pp. E792-E804 ◽  
Author(s):  
Xia Lei ◽  
Qing Li ◽  
Susana Rodriguez ◽  
Stefanie Y. Tan ◽  
Marcus M. Seldin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Mouse Models ◽  
Insulin Action ◽  
Thromboxane A2 ◽  
Whole Body ◽  
Thromboxane Synthase ◽  
Tissue Fibrosis ◽  
Obesity And Diabetes

Thromboxane A2, an arachidonic acid-derived eicosanoid generated by thromboxane synthase (TBXAS), plays critical roles in hemostasis and inflammation. However, the contribution of thromboxane A2 to obesity-linked metabolic dysfunction remains incompletely understood. Here, we used in vitro and mouse models to better define the role of TBXAS in metabolic homeostasis. We found that adipose expression of Tbxas and thromboxane A2 receptor ( Tbxa2r) was significantly upregulated in genetic and dietary mouse models of obesity and diabetes. Expression of Tbxas and Tbxa2r was detected in adipose stromal cells, including macrophages. Furthermore, stimulation of macrophages with interferon-γ or resistin factors known to be upregulated in obesity induced Tbxas and Tbxa2r expression. Mice lacking Tbxas had similar weight gain, food intake, and energy expenditure. However, loss of Tbxas markedly enhanced insulin sensitivity in mice fed a low-fat diet. Improvement in glucose homeostasis was correlated with the upregulated expression of multiple secreted metabolic regulators ( Ctrp3, Ctrp9, and Ctrp12) in the visceral fat depot. Following a challenge with a high-fat diet, Tbxas deficiency led to attenuated adipose tissue fibrosis and reduced circulating IL-6 levels without adipose tissue macrophages being affected; however, these changes were not sufficient to improve whole body insulin action. Together, our results highlight a novel, diet-dependent role for thromboxane A2 in modulating peripheral tissue insulin sensitivity and adipose tissue fibrosis.

Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue

2005 ◽  
Vol 288 (5) ◽  
pp. E957-E964 ◽  
Author(s):  
Galina Apostolova ◽  
Roberto A. S. Schweizer ◽  
Zoltan Balazs ◽  
Radina M. Kostadinova ◽  
Alex Odermatt
Keyword(s):  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Obesity And Diabetes ◽  
Promising Target ◽  
Pparγ Agonist ◽  
Treatment Of Obesity ◽  
Underlying Mechanisms

Dehydroepiandrosterone (DHEA) exerts beneficial effects on blood glucose levels and insulin sensitivity in obese rodents and humans, resembling the effects of peroxisome proliferator-activated receptor-γ (PPARγ) ligands and opposing those of glucocorticoids; however, the underlying mechanisms remain unclear. Glucocorticoids are reactivated locally by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which is currently considered as a promising target for the treatment of obesity and diabetes. Using differentiated 3T3-L1 adipocytes, we show that DHEA causes downregulation of 11β-HSD1 and dose-dependent reduction of its oxoreductase activity. The effects of DHEA were comparable with those of the PPARγ agonist rosiglitazone but not additive. Furthermore, DHEA reduced the expression of hexose-6-phosphate dehydrogenase, which stimulates the oxoreductase activity of 11β-HSD1. These findings were confirmed in white adipose tissue and in liver from DHEA-treated C57BL/6J mice. Analysis of the transcription factors involved in the DHEA-dependent regulation of 11β-HSD1 expression revealed a switch in CCAAT/enhancer-binding protein (C/EBP) expression. C/EBPα, a potent activator of 11β-HSD1 gene transcription, was downregulated in 3T3-L1 adipocytes and in liver and adipose tissue of DHEA-treated mice, whereas C/EBPβ and C/EBPδ, attenuating the effect of C/EBPα, were unchanged or elevated. Our results further suggest a protective effect of DHEA on adipose tissue by upregulating PPARα and downregulating leptin, thereby contributing to the reduced expression of 11β-HSD1. In summary, we provide evidence that some of the anti-diabetic effects of DHEA may be caused through inhibition of the local amplification of glucocorticoids by 11β-HSD1 in adipose tissue.

scholarly journals Different Effects of Leucine Supplementation and/or Exercise on Systemic Insulin Sensitivity in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofan Jiang ◽  
Yuwei Zhang ◽  
Weichao Hu ◽  
Yuxiu Liang ◽  
Liang Zheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Leucine Supplementation ◽  
Obesity Epidemic ◽  
Glut4 Expression ◽  
Systemic Insulin Resistance ◽  
Treatment Of Obesity ◽  
Simultaneous Intervention

ObjectiveObesity-related diseases such as diabetes, hypertension, dyslipidemia, and cardiovascular diseases have increased due to the obesity epidemic. Early intervention for obesity through lifestyle and nutrition plays an important role in preventing obesity-related diseases. Therefore, the purpose of this study is to explore the role of leucine and exercise in adiposity, systemic insulin resistance, and inflammation to provide theoretical and guiding basis for the early prevention and treatment of obesity.MethodsC57BL/6J male mice were randomly divided into HFD or LFD-fed mice group. After 9 weeks, glucose tolerance test (GTT) was performed to detect their systemic insulin sensitivity. Starting from week 10, mice were divided into eight groups and treated with moderate exercise or/and 1.5% leucine. At week 13, systemic insulin sensitivity was detected by GTT. At week 14, mice were dissected to analyze adiposity and inflammation.ResultsIn LFD mice, exercise significantly increased systemic insulin sensitivity by increasing GLUT4 expression in the muscle and decreasing adiposity through increasing AMPK phosphorylation in adipose tissue. In HFD mice, the simultaneous intervention of exercise and leucine increases systemic insulin sensitivity by reducing liver and adipose tissue inflammation via decreasing NF-κB p65 phosphorylation, and increasing the expression of adiponectin in adipose tissue.ConclusionThere are different mechanisms underlying the effects of exercise and leucine on insulin resistance and inflammation in LFD-fed mice or HFD-fed mice.

scholarly journals Activation of the Cholinergic Antiinflammatory Pathway Ameliorates Obesity-Induced Inflammation and Insulin Resistance

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 836-846 ◽  
Author(s):  
XianFeng Wang ◽  
ZhengGang Yang ◽  
Bingzhong Xue ◽  
Hang Shi
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Cytokine Production ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Tissue Macrophage ◽  
Therapeutic Benefits ◽  
Inflammatory State ◽  
Treatment Of Obesity

Obesity is associated with a chronic inflammatory state characterized by adipose tissue macrophage infiltration and inflammation, which contributes to insulin resistance. The cholinergic antiinflammatory pathway, which acts through the macrophage α7-nicotinic acetylcholine receptor (α7nAChR), is important in innate immunity. Here we show that adipose tissue possesses a functional cholinergic signaling pathway. Activating this pathway by nicotine in genetically obese (db/db) and diet-induced obese mice significantly improves glucose homeostasis and insulin sensitivity without changes of body weight. This is associated with suppressed adipose tissue inflammation. In addition, macrophages from α7nAChR−/− [α7 knockout (α7KO)] mice have elevated proinflammatory cytokine production in response to free fatty acids and TNFα, known agents causing inflammation and insulin resistance. Nicotine significantly suppressed free fatty acid- and TNFα-induced cytokine production in wild type (WT), but not α7KO macrophages. These data suggest that α7nAChR is important in mediating the antiinflammatory effect of nicotine. Indeed, inactivating this pathway in α7KO mice results in significantly increased adipose tissue infiltration of classically activated M1 macrophages and inflammation in α7KO mice than their WT littermates. As a result, α7KO mice exhibit more severely impaired insulin sensitivity than WT mice without changes of body weight. These data suggest that the cholinergic antiinflammatory pathway plays an important role in obesity-induced inflammation and insulin resistance. Targeting this pathway may provide novel therapeutic benefits in the prevention and treatment of obesity-induced inflammation and insulin resistance.

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