Propionate : a candidate metabolite to link colonic metabolism to human adipose tissue inflammation

Abstract

Obesity and its associated low-grade inflammation and pathological consequences, including insulin resistance and type-2 diabetes, pose a great challenge to the health systems nowadays. Adipose tissue is a primary site of obesity-induced inflammation which is emerging as an important contributor to the obesity-related diseases. The factors influencing adipose tissue-induced inflammation and the resulting pathologies remain poorly understood. However, dietary fiber diets appear to be protective, suggesting a cross-talk between the colonic metabolism and adipose tissue-induced inflammation. Short-chain fatty acids, e.g. propionic acid (PA), are the principal products of the dietary fiber fermentation by microbiota. Here we showed that the treatment of human omental adipose tissue with PA resulted in a significant downregulation of several inflammatory parameters and positively influenced factors associated with insulin sensitivity, adipogenesis and lipogenesis in this tissue via Gi/o-dependent and –independent mechanisms. Furthermore, we demonstrated that adipose tissue macrophages markers were either not detected or very low in adipocytes compared to adipose tissue. This implies that non-adipocyte cells contribute to the immunosuppressive effects of PA. Intriguingly, PA was shown to counteract the inflammation of human macrophages. Finally we revealed that adipocytes exhibit an immune cell like behavior and they contribute for the initiation of the inflammation independent of the macrophages. Our data provide a new paradigm in understanding the relation between the colonic metabolism and adipose tissue physiology and suggest that the modulation of PA quantity may have potential application in suppressing low-grade inflammation and protecting from its associated diseases, such as insulin resistance and type-2 diabetes.

	Titel en inhoud
	Hoofdstuk 1
	Hoofdstuk 2
	Hoofdstuk 3
	Hoofdstuk 4 (Embargo t/m 08-09-2011)
	Hoofdstuk 5 (Embargo t/m 08-09-2011)
	Hoofdstuk 6 (Embargo t/m 08-09-2011)
	Engelse samenvatting
	Nederlandse samenvatting
	Dankwoord
	Curriculum vitae
	Volledige dissertatie (Embargo t/m 08-09-2011)

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