Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice.
Sebastien Le GarfJoseph MurdacaIsabelle Mothe-SatneyBrigitte SibilleGwenaëlle Le MennGiulia ChinettiJaap G NeelsAnne-Sophie RousseauPublished in: International journal of molecular sciences (2019)
Regular aerobic exercise, independently of weight loss, improves metabolic and anti-inflammatory states, and can be regarded as beneficial in counteracting obesity-induced low-grade inflammation. However, it is still unknown how exercise alters immunometabolism in a context of dietary changes. Agonists of the Peroxisome Proliferator Activated-Receptor beta/delta (PPARβ/δ) have been studied this last decade as "exercise-mimetics", which are potential therapies for metabolic diseases. In this study, we address the question of whether PPARβ/δ agonist treatment would improve the immunometabolic changes induced by exercise in diet-induced obese female mice, having switched from a high fat diet to a normal diet. 24 mice were assigned to groups according to an 8-week exercise training program and/or an 8-week treatment with 3 mg/kg/day of GW0742, a PPARβ/δ agonist. Our results show metabolic changes of peripheral lymphoid tissues with PPARβ/δ agonist (increase in fatty acid oxidation gene expression) or exercise (increase in AMPK activity) and a potentiating effect of the combination of both on the percentage of anti-inflammatory Foxp3+ T cells. Those effects are associated with a decreased visceral adipose tissue mass and skeletal muscle inflammation (TNF-α, Il-6, Il-1β mRNA level), an increase in skeletal muscle oxidative capacities (citrate synthase activity, endurance capacity), and insulin sensitivity. We conclude that a therapeutic approach targeting the PPARβ/δ pathway would improve obesity treatment.
Keyphrases
- insulin resistance
- weight loss
- high fat diet induced
- skeletal muscle
- adipose tissue
- high fat diet
- high intensity
- metabolic syndrome
- bariatric surgery
- gene expression
- physical activity
- fatty acid
- low grade
- resistance training
- type diabetes
- anti inflammatory
- roux en y gastric bypass
- oxidative stress
- gastric bypass
- body mass index
- dna methylation
- weight gain
- rheumatoid arthritis
- high grade
- body composition
- nitric oxide
- regulatory t cells
- hydrogen peroxide
- glycemic control
- risk assessment
- smoking cessation
- protein kinase
- double blind