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Objective@#To explore the effect and mechanism of omega 3-polyunsaturated fatty acid(ω3-PUFA) dietary intervention on mitochondrial function of white adipose tissue in adult rats with postnatal early overfeeding.@*Methods@#An overfed animal model by adjusting litter size was developed for the study of neonatal overfeeding. The litter size was adjusted to 3 male rats per litter(small litter, SL group) and 10 pups per litter(normal litter, NL group). After weaning(week 3), the pups were fed standard chow or ω3-PUFA diet(SL-FO) until postnatal weeks 13. Food intake, body weight, and rectal temperature of rats were measured regularly, and energy metabolism of animals was monitored in week 13. During week 3 and 13, subcutaneous adipose tissue was collected. Inguinal preadipocytes of mice were isolated and induced to differentiate, and 50 μmol/L eicosapentaenoicacid(EPA) was administered for 48 h at the late stage of differentiation. The mRNA and protein expression levels of mitochondrial related genes, mitochondrial copy number, and oxygen consumption rate of adipocytes were detected in adipose tissue and adipocytes.@*Results@#By the 3rd week, the body weight, food intake, and fat cell area in SL group were higher than those in NL group while the body temperature was lower until to 13 weeks. By the 13th week, the O2 consumption, CO2 output, and heat production of rats in SL group were lower than those in NL group. Meanwhile, the expressions of mitochondrial function related genes such as uncoupling protein 1(UCP1), carnitine palmitoyltransferase 1(CPT1), SIRT1, and mitochondrial biosynthesis regulatory gene peroxisome proliferator-activated receptor coativator-1 (PGC1α) in adipose tissue by the 3rd and 13th week were significantly reduced(P<0.05). After weaning, ω3-PUFA diet significantly reduced weight gain in SL rats, increased UCP1 protein expression, restored energy metabolism level and mitochondrial function related gene expression. In vitro intervention of EPA increased the mitochondrial copy number, the mRNA and protein expression levels of mitochondrial biosynthesis and functional genes, as well as the mitochondrial basic oxygen consumption rate(P<0.05).@*Conclusion@#ω3-PUFA improves postnatal overfeeding-induced impairment of the mitochondrial function and biosynthesis of subcutaneous white adipose tissue in rats, which may be an important mechanism for fish oil diet to inhibit the early over-nutrition program and restore the thermogenic metabolism.
RESUMEN
Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats,and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding.Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table.After weaning at postnatal week 3,the rats were randomly given standard chow or high-fat (HF) diet until week 16.Hence four groups were analyzed,namely normal feeding group,breastfed overfeeding group,post-weaning overfeeding group,and continuous overfeeding group.Body weight was continuously monitored in each week.Visceral fat pad (retroperitoneal and perigenital),systolic pressure,and heart rate were observed at week 3 and week 16.Thoracic aorta was sampled for measurement of vascular endothelial dilation function.Histological morphology was observed with HE staining,nitric oxide content of thoracic aorta was detected with nitrate reductase method.The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction.The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot.Results At week 3,breastfed overfeeding rats displayed significantly larger body weight [(77.80 ± 0.57) g vs.(62.80 ±0.85) g,t =14.576,P ＜ 0.01] and visceral fat [retroperitoneal:(8.19 ± 0.49) mg/g vs.(4.92 ± 0.31) mg/g,t =5.629,P＜0.01;perigenital:(3.50 ±0.29) mg/g vs.(2.08 ±0.13) mg/g,t =4.552,P ＜0.01] compared with normal feedindg rats,and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F =15.215,P ＜0.01);high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats.At week 16,continuous overfeeding rats showed hypertension [(149 ± 1.94) mmHg (1 mmHg =0.133 kPa),F =22.834,P ＜0.01],impaired vascular endothelial dilation function (F =7.648,P ＜ 0.05),and reduced protein expression of phosphorylated eNOS (F =15.215,P ＜ 0.01),while the post-weaning overfeeding group only had elevated blood pressure.Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension.The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding.