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Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies.

ABSTRACT: Obesity-associated type 2 diabetes mellitus (T2DM) is characterized by low-grade chronic systemic inflammation that arises primarily from the white adipose tissue. The interplay between various adipose tissue-derived chemokines drives insulin resistance in T2DM and has therefore become a subject of rigorous investigation. The adipocytokines strongly associated with glucose homeostasis include tumor necrosis factor-?, various interleukins, monocyte chemoattractant protein-1, adiponectin, and leptin, among others. Remodeling the adipose tissue inflammasome in obesity-associated T2DM is likely to treat the underlying cause of the disease and bring significant therapeutic benefit. Various strategies have been adopted or are being investigated to modulate the serum/tissue levels of pro- and anti-inflammatory adipocytokines to improve glucose homeostasis in T2DM. These include use of small molecule agonists/inhibitors, mimetics, antibodies, gene therapy, and other novel formulations. Here, we discuss adipocytokines that are strongly associated with insulin activity and therapies that are under investigation for modulation of their levels in the treatment of T2DM.

SUBMITTER: Banerjee A

PROVIDER: S-EPMC7237149 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies.

Banerjee Amrita A Singh Jagdish J

Bioengineering & translational medicine 20191213 2

Obesity-associated type 2 diabetes mellitus (T2DM) is characterized by low-grade chronic systemic inflammation that arises primarily from the white adipose tissue. The interplay between various adipose tissue-derived chemokines drives insulin resistance in T2DM and has therefore become a subject of rigorous investigation. The adipocytokines strongly associated with glucose homeostasis include tumor necrosis factor-α, various interleukins, monocyte chemoattractant protein-1, adiponectin, and lept ...[more]

PMID: 32440558

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Project description:Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-inflammatory cytokines interleukin (IL)-1? and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed significantly increased proliferation and differentiation. We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products, i.e., IL-1 family members such as IL-1? and IL-18 were upregulated in the PVAT of obese mini pigs; PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid. Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.

Dataset Information

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies.

Publications

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies.

Similar Datasets

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