Indomethacin Treatment Prevents High Fat Diet-induced Obesity and Insulin Resistance but Not Glucose Intolerance in C57BL/6J Mice

Abstract

Background: Obesity-associated insulin resistance is linked to inflammation. Results: Indomethacin, an anti-inflammatory cyclooxygenase inhibitor, prevented diet-induced obesity, but mice became glucose-intolerant with sustained hepatic glucose output and impaired glucose-stimulated insulin secretion. Conclusion: Inhibition of cyclooxygenase activity alters the metabolic consequences of an obesogenic high fat diet. Significance: Intake of anti-inflammatory cyclooxygenase inhibitors may impair glucose tolerance.

Impact of dietary ω3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function

“…The complexity of this system becomes apparent in IP receptor knockout mice, which are protected from ω6 PUFA-induced body and fat mass gain (16). In a similar way, when mice were fed a high fat diet, the inhibition of COX activities with indomethacin prevented body weight gain, due to decreased fat storage and enhanced recruitment of brite adipocytes in the scWAT (15,43). These examples emphasize the need to increase our current understanding of the proand anti-adipogenic properties of PUFAs on the level of oxylipin metabolism to modulate energy balance regulation.…”

“…The obesogenic effect of ω6 PUFAs, particularly ARA, is thought to originate from their metabolization to oxylipins thus promoting fat storage and a reduction in energy expenditure (16,17,43,44). However, this system and its regulation appear to underlie an unanticipated complexity.…”

Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin-resistant, obesity-prone rats

“…The altered production of oxygenated, bioactive polyunsaturated fatty acids (PUFAs) (i.e., oxylipins) in obesity may have pathological consequences, and a number of recent studies have investigated the mediation of obesity-induced insulin resistance by oxylipins [5][6][7][8][9]. Oxylipins include a myriad of species derived from n6 PUFA, such as arachidonic acid (ArA; 20:4n6) and linoleic acid (LA; 18:2n6), and from n3 PUFA, such as α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), and docosahexaenoic acid (DHA; 22:6n3).…”

Acide arachidonique et prostaglandines : impact sur la formation des adipocytes blancs, bruns et brites/beiges

“…Par contre, un rôle opposé de la même voie a été décrit récemment chez des souris C57BL/6J (une souche sensible aux régimes riches en graisses) [47]. Dans ce dernier cas, lorsque les souris ont été nourries avec un régime riche en graisses, l'inhibition de l'activité cyclooxygénase limite la prise de poids, ce qui est dû, en partie, au recrutement d'adipocytes brites dans le TAB sous-cutané [47]. Les données obtenues avec la même souche de souris C57BL/6 nourries avec un régime supplémenté en ARA sont en accord avec cette dernière observation [44].…”