Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation

Abstract

Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut.

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring

“…TAS1R1 and TAS1R3 form a heterodimer which detects umami taste, and TAS1R3 can also form a heterodimer with TAS1R2 to detect sweet taste ( 55 , 56 ). We were recently the first to report that offspring at weaning from HF-fed mothers have increased expression of Tas1r1 and reduced expression of Tas1r3 in the gut compared with offspring from CD mothers ( 57 ). In line with these findings, there was a significant interaction between maternal HF and salt on gut Tas1r1 expression in the gut of adult male offspring.…”

Long-term effects of a maternal high-fat: high-fructose diet on offspring growth and metabolism and impact of maternal taurine supplementation

“…We have previously shown that a MO diet leads to early onset of puberty in male and female offspring that is associated with increased weight at weaning, hyperleptinemia and increased fat mass in the immediate pre-pubertal period. [29][30][31][32] In the current…”

Inhibitory Effect of Methotrexate on Rheumatoid Arthritis Inflammation and Comprehensive Metabolomics Analysis Using Ultra-Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (UPLC-Q/TOF-MS)

“…A lower level of linoleic acid reported before in RA serum is consistent with our results in CIA [ 34 ]. Linoleic acid also has the potential to ameliorate the high expression level of NLRP3 genes and reduced the release of mature IL-1β and other cytokines [ 35 , 36 ]. Despite that methotrexate could damage the dietary absorption of linoleic acid [ 37 ], it had already been reported to increase linoleic acid in carcinoma cell and was demonstrated in present study in CIA rats to play its anti-inflammation role [ 38 ].…”