Anti-Obesity and Anti-Hyperglycemic Effects of Cinnamaldehyde via altered Ghrelin Secretion and Functional impact on Food Intake and Gastric Emptying

Abstract

Cinnamon extract is associated to different health benefits but the active ingredients or pathways are unknown. Cinnamaldehyde (CIN) imparts the characteristic flavor to cinnamon and is known to be the main agonist of transient receptor potential-ankyrin receptor 1 (TRPA1). Here, expression of TRPA1 in epithelial mouse stomach cells is described. After receiving a single-dose of CIN, mice significantly reduce cumulative food intake and gastric emptying rates. Co-localization of TRPA1 and ghrelin in enteroendocrine cells of the duodenum is observed both in vivo and in the MGN3-1 cell line, a ghrelin secreting cell model, where incubation with CIN up-regulates expression of TRPA1 and Insulin receptor genes. Ghrelin secreted in the culture medium was quantified following CIN stimulation and we observe that octanoyl and total ghrelin are significantly lower than in control conditions. Additionally, obese mice fed for five weeks with CIN-containing diet significantly reduce their cumulative body weight gain and improve glucose tolerance without detectable modification of insulin secretion. Finally, in adipose tissue up-regulation of genes related to fatty acid oxidation was observed. Taken together, the results confirm anti-hyperglycemic and anti-obesity effects of CIN opening a new approach to investigate how certain spice derived compounds regulate endogenous ghrelin release for therapeutic intervention.

Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming

“…5). Previous studies have shown that long-term CA supplementation in food can protect mice from diet-induced obesity and hyperglycemia [3, 7]. In vitro , upon chronic treatment with CA, Fgf21 and Ucp1 were significantly upregulated in both murine inguinal adipocytes and human subcutaneous fat cultures (Supplemental Fig.…”

“…While the beneficial effects of CA on systemic metabolism have recently been observed [3, 4, 7], the underlying molecular basis of these effects remains largely unknown. To explore the possibility that CA influences whole body metabolism through direct action on adipocytes, we treated fully differentiated adipocytes isolated from the murine inguinal subcutaneous fat depot with CA.…”

“…Previous studies have shown that cinnamaldehyde (CA), an essential oil found in cinnamon, can reduce diet-induced weight gain and improve glucose homeostasis when given to mice as a supplement in food [3, 4]. Interestingly, cinnamon consumption has also been reported to correlate with lower levels of fasting blood glucose in human studies [5].…”

Structure–activity relationships of the prototypical TRPM8 agonist icilin

“…12 These findings suggest the potential relevance of icilin and 'icilin-like' compounds as therapeutic strategy for the treatment of a variety of pathological conditions. Although Wei 13 and Foster, et al 14 made some further investigations into variations of the icilin structure, they did not report either the potency of their compounds (EC 50 ) or their selectivity.…”

“…Some compounds (compounds 11) with a contracted central ring were prepared by a modification of this approach 16 (Scheme 2). The rigid analogs, 16, were prepared by the original pathway utilizing tetralone (12) or 5-nitro-or 7-nitro-tetralone (13) as the starting material 17 (Scheme 3).…”