1759-P: Prostaglandin PGE2 Receptor EP4 Signaling Deficiency in Microglia Reduces Weight Gain with Transient Glucose Improvements in Diet-Induced Obesity

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1759-P
Author(s):  
ANZELA NIRAULA ◽  
RACHAEL FASNACHT ◽  
KELLY M. NESS ◽  
JEREMY FREY ◽  
MAURICIO D. DORFMAN ◽  
...  
Keyword(s):  
Weight Gain ◽  
Diet Induced Obesity ◽  
Pge2 Receptor

scholarly journals Prostaglandin PGE2 receptor EP4 regulates microglial phagocytosis and increases susceptibility to diet-induced obesity

2021 ◽  
Author(s):  
Anzela Niraula ◽  
Rachael D Fasnacht ◽  
Kelly M Ness ◽  
Jeremy M Frey ◽  
Mauricio D Dorfman ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Microglial Activation ◽  
Body Weight Gain ◽  
Microglial Phagocytosis ◽  
Diet Induced Obesity ◽  
Insulin Tolerance ◽  
Pge2 Receptor

Background: In rodents, susceptibility to diet-induced obesity requires microglial activation, but the molecular components of this pathway remain incompletely defined. Prostaglandin E2 (PGE2) levels increase in the mediobasal hypothalamus during high fat diet (HFD) feeding, and the PGE2 receptor EP4 regulates microglial activation state and phagocytic activity, suggesting a potential role for microglial EP4 signaling in obesity pathogenesis. Method: Metabolic phenotyping, as assessed by body weight, energy expenditure, glucose, and insulin tolerance, was performed in microglia-specific EP4 knockout (MG-EP4 KO) mice and littermate controls on HFD. Morphological and gene expression analysis of microglia, and a histological survey of microglia-neuron interactions in the arcuate nucleus was performed. Phagocytosis was assessed using in vivo and in vitro pharmacological techniques. Results: Microglial EP4 deletion markedly reduced weight gain and food intake in response to HFD feeding. In correspondence with this lean phenotype, insulin sensitivity was also improved in the HFD-fed MG-EP4 KO mice though glucose tolerance remained surprisingly unaffected. Mechanistically, EP4-deficient microglia showed an attenuated phagocytic state marked by reduced CD68 expression and fewer contacts with POMC neuron soma and processes. These cellular changes observed in the microglial EP4 knockout mice corresponded with an increased density of POMC neurites extending into the paraventricular nucleus. Conclusion: These findings reveal that microglial EP4 signaling promotes body weight gain and insulin resistance during HFD feeding. Furthermore, the data suggest that curbing microglial phagocytic function may preserve POMC cytoarchitecture and PVN input to limit overconsumption during diet-induced obesity.

Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Phetcharat Chen ◽  
Christina Park ◽  
Eltayeb Karrar ◽  
Chaoyung Wang ◽  
James Liao
Keyword(s):  
Weight Gain ◽  
Body Temperature ◽  
Cold Exposure ◽  
Diet Induced Obesity ◽  
Therapeutic Benefits ◽  
White Adipocytes ◽  
Important Regulator ◽  
And Function ◽  
White Fat ◽  
Adipocyte Development

Background: The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown. Methods and Result: To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2 adipoQ-/- ) and overexpression (CA-ROCK adipoQ+/+ ) of ROCK2 in mice. Compared to control mice, CA-ROCK adipoQ+/+ mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK adipoQ+/+ mice showed that UCP1 was upregulated. Furthermore, CA-ROCK adipoQ+/+ mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2 adipoQ-/- mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2 adipoQ-/- mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2 adipoQ-/- mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2 adipoQ-/- mice. Thermal imaging revealed that ROCK2 adipoQ-/- mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK adipoQ+/+ mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates. Conclusions: ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.

Extract of Irish potatoes (Solanum tuberosumL.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity

2014 ◽  
Vol 58 (11) ◽  
pp. 2235-2238 ◽  
Author(s):  
Stan Kubow ◽  
Luc Hobson ◽  
Michèle M. Iskandar ◽  
Kebba Sabally ◽  
Danielle J. Donnelly ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Mouse Model ◽  
Glucose Control ◽  
Body Weight Gain ◽  
Diet Induced Obesity

scholarly journals Effects of Melatonin on Lipid Metabolism and Circulating Irisin in Sprague-Dawley Rats with Diet-Induced Obesity

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3329
Author(s):  
Yu-Tang Tung ◽  
Pei-Chin Chiang ◽  
Ya-Ling Chen ◽  
Yi-Wen Chien
Keyword(s):  
Weight Gain ◽  
Total Cholesterol ◽  
Vehicle Control ◽  
Serum Total Cholesterol ◽  
Sprague Dawley ◽  
High Fat ◽  
Melatonin Treatment ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Cholesterol Excretion

Melatonin, a pivotal photoperiodic signal transducer, may work as a brown-fat inducer that regulates energy balance. Our study aimed to investigate the effects of melatonin treatment on the body fat accumulation, lipid profiles, and circulating irisin of rats with high-fat diet-induced obesity (DIO). Methods: 30 male Sprague-Dawley rats were divided into five groups and treated for 8 weeks: vehicle control (VC), positive control (PC), MEL10 (10 mg melatonin/kg body weight (BW)), MEL20 (20 mg/kg BW), and MEL50 (50 mg/kg BW). The vehicle control group was fed a control diet, and the other groups were fed a high-fat and high-calorie diet for 8 weeks to induce obesity before the melatonin treatment began. Melatonin reduced weight gain without affecting the food intake, reduced the serum total cholesterol level, enhanced the fecal cholesterol excretion, and increased the circulating irisin level. Melatonin downregulated the fibronectin type III domain containing 5 (FNDC5) and lipoprotein lipase (LPL) mRNA expressions of inguinal white adipose tissue (iWAT) and induced the browning of iWAT in both the MEL10 and MEL20 groups. Conclusion: Chronic continuous melatonin administration in drinking water reduced weight gain and the serum total cholesterol levels. Additionally, it enhanced the circulating irisin, which promoted brite/beige adipocyte recruitment together with cholesterol excretion and contributed to an anti-obesity effect.

scholarly journals Leptin resistance: a prediposing factor for diet-induced obesity

2009 ◽  
Vol 296 (3) ◽  
pp. R493-R500 ◽  
Author(s):  
Philip J. Scarpace ◽  
Yi Zhang
Keyword(s):  
Weight Gain ◽  
Leptin Receptor ◽  
Causative Factor ◽  
Leptin Resistance ◽  
Chow Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Dietary Fructose ◽  
Complex Chronic Disease ◽  
Obesity Syndrome

Obesity is a resilient and complex chronic disease. One potential causative factor in the obesity syndrome is leptin resistance. Leptin behaves as a potent anorexic and energy-enhancing hormone in most young or lean animals, but its effects are diminished or lacking in the obese state associated with a normal genetic background. Emerging evidence suggests that leptin resistance predisposes the animal to exacerbated diet-induced obesity (DIO). Elevation of central leptin in young, lean rats induces a leptin resistance that precludes obesity on a chow diet but accelerates high-fat (HF)-induced obesity. Similarly, chronic dietary fructose consumption evokes a leptin resistance that causes obesity only upon HF exposure. Inherent central leptin insensitivity also contributes to dietary weight gain in certain obesity-prone rats. Conversely, aged, leptin-resistant animals are obese with continuous chow feeding and demonstrate aggravated obesity when challenged with an HF diet. Additionally, a submaximal central blockade with a leptin antagonist leads to obesity on both chow and HF diets, as is the case in rodents with leptin receptor deficiency of genetic origin. Despite the differences in the incidence of obesity on a chow diet, all of these forms of leptin resistance predispose rodents to aggravated HF-mediated obesity. Moreover, once leptin resistance takes hold, it aggravates DIO, and the leptin resistance and obesity compound one another, promoting a vicious cycle of escalating weight gain.

scholarly journals Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

2013 ◽  
Vol 305 (3) ◽  
pp. E439-E450 ◽  
Author(s):  
Ping Kong ◽  
Carlos Gonzalez-Quesada ◽  
Na Li ◽  
Michele Cavalera ◽  
Dong-Wook Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Uptake ◽  
Cytokine Signaling ◽  
Vascular Density ◽  
Acid Uptake ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes.

scholarly journals Kappa-Carrageenan Inhibited the High-Fat-Diet-Induced Obesity Through Up-Regulating the Hepatic Sirt1 Gene Expression

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 503-503
Author(s):  
Zhiji Huang ◽  
Yafang Ma ◽  
Chunbao Li
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Energy Intake ◽  
High Fat Diet ◽  
The Body ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Sirt1 Gene ◽  
Kappa Carrageenan

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake.  The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

scholarly journals Bauhiniastatin-1 alleviates diet induced obesity and lipid accumulation through modulating PPAR-γ/AMPK expressions: In-vitro, in-vivo and in-silico studies.

2021 ◽  
Author(s):  
Karunakaran Reddy Sankaran ◽  
Lokanatha Oruganti ◽  
Muni Swamy Ganjayi ◽  
Venkataramaiah Chintha ◽  
Muni Kesavulu Muppuru ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Western Blot ◽  
Blot Analysis ◽  
Body Weight Gain ◽  
Liver Lipid ◽  
Ppar Γ ◽  
Diet Induced Obesity

Abstract Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).

scholarly journals Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

2021 ◽  
Author(s):  
Camila Queiroz-Glauss ◽  
Mariana Vieira ◽  
Marcela Helena Gonçalves-Pereira ◽  
Stephanie Almeida ◽  
Rachel Freire ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Experimental Studies ◽  
Treg Cells ◽  
Loss Of Function ◽  
High Fat ◽  
Diet Induced Obesity ◽  
And Function

Background: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms induced by the parasite that regulate the development of metabolic diseases in the host are unclear. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal Findings: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by higher levels of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also revert the loss of function in Tregs associated with high fat diet. Conclusion: These data suggest that H. polygyrus infection can prevent weight gain and metabolic syndrome in animals fed with high fat diet associated with modulations of adipose tissue Treg cells.

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