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

PhD ceremony: Mr. S.H.M. Al-Lahham, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

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

Promotor(s): prof. R.J. Vonk

Faculty: Medical Sciences

Obesity and its associated low-grade inflammation and pathological consequences, including insulin resistance and type-2 diabetes, pose a great challenge to the health system 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 appears 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 the microbiota. Here we showed that the treatment of human omental adipose tissue with PA resulted in a significant down-regulation of several inflammatory parameters and positively influenced factors associated with insulin sensitivity, adipogenesis and lipogenesis in this tissue. Furthermore, we demonstrated that adipose tissue macrophages markers were either not detected or very low in cultured adipocytes compared to ex vivo cultured 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 that they contribute to 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.