Targeting adipose tissue in the treatment of obesity-associated diabetes

Kusminski, Christine M.; Bickel, Perry E.; Scherer, Philipp E.

doi:10.1038/nrd.2016.75

Cited by 544 publications

(457 citation statements)

References 303 publications

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“…It was estimated that about 300,000 people die each year from obesity and related causes, which puts this disorder as the second leading cause of death. In fact, being both overweight and obese increases the risk of several diseases and health conditions such as high triglycerides, cholesterol, diabetes, heart disease, high blood pressure, tumors (breast, colon, and endometrial), sleep disorders, and respiratory problems [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the antiobesity and antioxidant properties of wild Plumbago europaea and Plumbago auriculata from North Palestine

Jaradat

Zaid

Hussein

2016

Chem. Biol. Technol. Agric.

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Background: Historically, plants have proven their value as a source of phytochemicals with therapeutic potentials and recently they play an important role in the discovery of novel drugs. Objectives:The current study aimed to investigate new antiobesity drugs from Plumbago europaea and Plumbago auriculata through the inhibition of the adsorption of dietary lipids. In vitro porcine pancreatic lipase inhibitory tests were conducted with weight reduction property as well as this study aimed to explore the antioxidant potential and to estimate total phenolic, flavonoid, and tannin contents in both of the studied species.Methods: Antioxidant capacity was evaluated using ferric reducing antioxidant power and DPPH assays, and porcine pancreatic lipase inhibitory tests were conducted using the UV spectrophotometric method, while total flavonoid, phenol, and tannin contents were estimated using standard phytochemical analytical methods.Results: Antioxidant potential and total flavonoid, phenol, and tannin contents of P. europaea were significantly higher than those of P. auriculata, and both of the studied species have potential antiobesity activity in comparison with orlistat. Conclusion:Results of the present study show that both of the studied Plumbago species consist of bioactive compounds that can act as lipase inhibitors and therefore can be useful for the development of functional foods against obesity. It can also be used as a source of lead compounds for designing new antiobesity drugs. Further isolation, identification, and characterization of phyto-active compounds responsible for antiobesity action are required to evaluate the full therapeutic potentials of these plants.

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Section: Introductionmentioning

confidence: 99%

Investigation of the antiobesity and antioxidant properties of wild Plumbago europaea and Plumbago auriculata from North Palestine

Jaradat

Zaid

Hussein

2016

Chem. Biol. Technol. Agric.

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“…Adiponectin is an adipocyte-derived hormone that displays a range of beneficial cardiometabolic properties including anti-inflammatory and insulin sensitizing effects [283,295]. Paradoxically, circulating adiponectin levels are reduced in obesity and this 'hypoadiponectinemia' contributes to the aetiology of obesity-associated diseases [283,295]. Consistent with this, humans with genetic polymorphisms that reduce adiponectin production and mice lacking adiponectin typically develop cardiovascular dysfunction and or type 2 diabetes [252,283].…”

Section: Introductionmentioning

confidence: 66%

“…The increase in prevalence and severity of obesity related cardiometabolic diseases continues to drive efforts to identify novel and efficacious therapeutic approaches [295]. One such strategy is to identify pharmacological approaches to increase adiponectin production [283].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The global prevalence of obesity-associated cardiometabolic diseases requires the development of novel therapeutic approaches [295,305]. Adiponectin is an adipocyte-derived hormone that displays a range of beneficial cardiometabolic properties including anti-inflammatory and insulin sensitizing effects [283,295].…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Yang¹

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The prevalence of obesity is growing at an alarming rate worldwide, and current therapies have limited benefits. Therefore, it is essential to increase our understanding of the underlying mechanisms so that new strategies can be developed to reduce the incidence of obesity related diseases. Adiponectin is an adipocyte-derived hormone that regulates glucose and lipid metabolism via direct and indirect mechanisms and has anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. Hypoadiponectinemia is implicated in the aetiology of obesity-related diseases making strategies to increase circulating adiponectin levels therapeutically attractive.Emerging evidence, predominantly from preclinical studies, suggests induction of heme-oxygenase-1 (HO-1) increases adiponectin production concomitant with decreased inflammatory tone prompting the proposal of a "HO-1 -adiponectin axis." However, the underlying mechanisms of increased adiponectin production via HO-1 induction are poorly defined; indeed a direct relationship has not been demonstrated. Thus, the overarching aim of this thesis is to investigate the effects of HO-1 induction on adiponectin production as well as adipocyte and adipose tissue remodelling and metabolic parameters using cellular and mouse models.Initial studies were designed to characterize the direct effect of HO-1 induction on adiponectin production. We found that treatment with the widely used HO-1 inducer cobalt protoporphyrin (CoPP) or hemin for 24-48 h increased HO-1 expression and activity without affecting adiponectin expression and secretion, in human mature adipocyte under a variety of experimental scenarios.Treatment of adipocytes with TNFα reduced adiponectin production and induced pro-inflammatory cytokines production. HO-1 induction failed to reverse these effects. These results do not support a direct HO-1 -adiponectin axis.However, literature suggests that chronic induction of HO-1 via CoPP administration throughout differentiation, promotes adiponectin secretion, albeit in the context of reduced adipogenesis. While our previous findings argued against the existence of a direct "HO-1 -adiponectin axis," they did not address the potential effects of chronic induction of HO-1 on adiponectin production. Thus, we extended our study to characterise the effects of chronic HO-1 induction throughout differentiation of human preadipocytes. In this study we demonstrate that chronic induction of HO-1 with CoPP or hemin throughout differentiation results in dose-dependent inhibition of adipogenesis and adiponectin production as well as induction of additional NRF2 target genes. Co-treatment with SnMP (HO-1 activity inhibitor) and HO-1 siRNA did not prevent these effects. These findings suggest that the chronic treatment with CoPP or hemin inhibits adipogenesis and adiponectin production potentially by a HO-1-independent mechanism that may be downstream of NRF2.iii However, our results contradict the majority of reports in the literature. One possibility is that the ...

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Potential Effects of Bariatric Surgery and Reduced Interleukin 32 Levels on Type 2 Diabetes and Its Comorbidities

Vita

2018

JAMA Pediatr

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Targeting adipose tissue in the treatment of obesity-associated diabetes

Cited by 544 publications

References 303 publications

Investigation of the antiobesity and antioxidant properties of wild Plumbago europaea and Plumbago auriculata from North Palestine

Investigation of the antiobesity and antioxidant properties of wild Plumbago europaea and Plumbago auriculata from North Palestine

Characterisation of the relationship between Heme-oxygenase-1 and adiponectin

Potential Effects of Bariatric Surgery and Reduced Interleukin 32 Levels on Type 2 Diabetes and Its Comorbidities

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