UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Madsen, Lise; Pedersen, Lone Møller; Lillefosse, Haldis Haukaas; Fjære, Even; Brønstad, Ingeborg; Qin, Hao; Petersen, Rasmus Koefoed; Hallenborg, Philip; Ma, Tao; Matteis, Rita De; Araujo, Pedro; Mercader, Josep M.; Bonet, M. Luisa; Hansen, Jacob B.; Cannon, Barbara; Nedergaard, Jan; Wang, Jun; Cinti, Saverio; Voshol, Peter J.; Døskeland, Stein Ove; Kristiansen, Karsten

doi:10.1371/journal.pone.0011391

Cited by 182 publications

(176 citation statements)

References 59 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…S1). Rosi and PGE2 have adipose tissue browning effects, which can induce adipose tissue transformation and angiogenesis (17,21). The NPs containing Rosi have an average size of 100 nm ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Rosi has been reported to stimulate PPAR activity, which leads not only to adipose tissue transformation by increasing the expression levels of uncoupling proteins but also activates angiogenesis in adipose tissue by elevating expression levels of VEGF and angiopoietin-like 4 (14)(15)(16). PGE2 has been shown to activate the prostaglandin receptor, which promotes adipose tissue transformation by increasing the expression of Uncoupling protein 1 (UCP1) (17). We show that peptide-conjugated NPs effectively deliver Rosi and PGE2 into adipose tissues while minimizing adverse effects on other tissues.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

Xue

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

150

View full text Add to dashboard Cite

The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

Xue

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

150

View full text Add to dashboard Cite

show abstract

“…Recent studies [44,45] demonstrated the involvement of COX-2 in the induction of these fatburning cells and the importance of the COX-2-mediated mechanisms for the resistance to dietary obesity in mice. Our results convincingly demonstrate a marked induction of mitochondrial oxidative capacity in permeabilised adipocytes isolated from epididymal fat in response to mild calorie restriction combined with LC n-3 PUFA intake, using succinate as the optimum fuel [46].…”

Section: Discussionmentioning

confidence: 99%

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

et al. 2011

View full text Add to dashboard Cite

Aims/hypothesis Calorie restriction is an essential component in the treatment of obesity and associated diseases. Longchain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. Methods Male mice (C57BL/6J) were habituated to a cornoil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF+F), ad libitum; (3) cHF with calorie restriction (CR; cHF+CR); and (4) cHF+F+CR. Mice fed a chow diet were also studied. Results We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ 12,15 -prostaglandin J 2 and protectin D1. Conclusions/interpretation White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.

show abstract

“…Parts of the eWAT were subjected to standard hematoxylin and eosin staining as described previously (40).…”

Section: Methodsmentioning

confidence: 99%

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

Liaset¹,

Qin

Jørgensen

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from dietinduced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1␣, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferatoractivated receptor ␤/␦ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome.

show abstract

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Cited by 182 publications

References 59 publications

Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome

Contact Info

Product

Resources

About