Study On The Functions Of Long-Chain Polyunsaturated Fatty Acids And Extensively Hydrolyzed Casein In White Adipose Tissue Browning

Browning of adipose tissues,which can be affected by diet,may mitigate the detrimental effects of adiposity and improve longer-term metabolic health.Here,browning-inducing effects of long-chain polyunsaturated fatty acids,e.g.,arachidonic acid（ARA）/docosahexaenoic acid（DHA）and extensively hydrolyzed casein（e HC）were investigated using uncoupling protein 1（UCP-1）luciferase reporter mice.To address the overall functionality,their potential role in supporting a healthy metabolic profile under obesogenic dietary challenges later in life was evaluated.At weaning Ucp1^+/LUC reporter mice were fed a control low fat diet（LFD）with or without ARA+DHA,e HC or e HC+ARA+DHA for 8 weeks until week 12after which interventions continued for another 12 weeks under a high-fat diet（HFD）challenge.Serological analysis（metabolic responses and inflammation）and in vivo and ex vivo luciferase activity were determined;in the meantime browning-contributing proteins UCP-1 and the key regulataory genes such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha（Pgc1α）and PR domain containing 16（Prdm16）were examined.ARA+DHA,e HC or their combination reduced body weight gain and adipose tissue weights compared to the HFD mice.The interventions induced UCP-1 expression in adipose tissues prior to and during the HFD exposure.UCP-1 induction was accompanied by higher PGC1αand PRDM16 expression.Glucose tolerance and insulin sensitivity were improved coinciding with lower serum cholesterol,triglycerides,free fatty acids,insulin,leptin,resistin,fibroblast growth factor 21,alanine aminotransferase,aspartate aminotransferase and higher adiponectin than the HFD group.HFD-associated increased systemic（IL-1βand TNF-α）and adipose tissue inflammation（F4/80,IL-1β,TNF-α,IL-6）were reduced.Studies in a UCP1-LUC reporter mouse model revealed that early intervention with ARA/DHA and e HC improve metabolic flexibility and attenuate obesity during HFD challenge later in life.Increased browning is suggested,at least partially,as the underlying mechanism.