Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation

Abstract

Background: Maternal obesity is an emerging problem in the modern world. Growing evidence suggests that intrauterine high-fat (HF) exposure may predispose progeny to subsequent metabolic challenges. Progeny born to mothers who ate an HF diet also tends to eat an HF diet when growing and aggravate metabolic issues. Thus, the generational transmission of obesity is cyclical. Developing a strategy to prevent the occurrence of metabolic syndrome related to prenatal and/or postnatal HF diet is important. In this study, the reprogramming effects of maternal resveratrol treatment for the progeny with maternal HF/postnatal HF diets were investigated. Methods: Sprague-Dawley dams were fed either a control or a high-fat/high sucrose diet (HFHS) from mating to lactation. After weaning, the progeny was fed chow or an HF diet. Four experimental groups were yielded: CC (maternal/postnatal control diet), HC (maternal HF/postnatal control diet), CH (maternal control/postnatal HFHS diet), and HH (maternal/postnatal HFHS diet). A fifth group (HRH) received a maternal HFHS diet plus maternal resveratrol treatment and a postnatal chow diet to study the effects of maternal resveratrol therapy.

Effects of Maternal Resveratrol Intake on the Metabolic Health of the Offspring

“…Different early life insults, such as maternal gestational diabetes (MGD), obesity and nutritional imbalances, have been used to study the potential protective effects of resveratrol. As summarized in Table 1 , the most commonly used experimental models for these studies involve rodents [ 13 , 29 , 30 , 31 , 61 , 65 , 66 , 67 , 68 , 69 ]. However, in an attempt to approximate human physiology, some studies have also been performed in nonhuman primates [ 62 , 63 , 64 ].…”

“…We used a Wistar rat model where dams received a low-fat diet (LFD; 10.2% Kcal from fat) or HFD (61.6% Kcal from fat) during gestation and lactation to determine the effect of maternal resveratrol intake (2–2.5 mg/kg/day in drinking water) during pregnancy and lactation on the metabolism of the offspring at weaning and observed that these effects depend on the type of diet ingested by the mother and the offspring’s sex [ 30 ]. Of note, we used a low dose of resveratrol that can be easily ingested in a normal diet and based on its described hormetic property [ 24 , 69 ]. We found that resveratrol decreased body weight (BW) and adipose tissue (visceral and subcutaneous) mass at weaning in offspring from HFD-fed dams but had no effect on these parameters in the offspring from LFD-fed dams.…”

“…In Sprague Dawley rats, Liu Ta-Yu and colleagues investigated the effects of resveratrol, administered in drinking water (50 mg/L), and maternal HFD intake on the progeny and the response to postnatal HFD intake. They reported that on PND140, maternal resveratrol intake reduced lipogenesis and adiposity, increased lipolysis and ameliorated leptin resistance in male progeny [ 69 ]. They also found that maternal resveratrol protected against the maternal high-fat/high-sucrose-induced decrease in SIRT1 mRNA levels in retroperitoneal adipose tissue and normalized the plasmatic leptin/sOB-R ratio of the offspring.…”

“…Interestingly, maternal resveratrol intake shifted the distribution of VAT adipocyte size to a significantly higher incidence of large adipocytes, regardless of sex or maternal diet [ 31 ], suggesting an effect on adipocyte development. Liu Ta-Yu reported a decrease in visceral adipocyte size in 4-month-old male progeny from dams fed a HFHSD plus resveratrol [ 69 ]. In Sprague Dawley rats, maternal resveratrol supplementation (50 mg/L in drinking water, from pregnancy to lactation) is also reported to reduce the maternal HFD-induced retroperitoneal adiposity and the increase in leptin/sOB-R ratio in adult male offspring, while no data in females were reported.…”

Effect of Polyphenols Intake on Obesity-induced Maternal Programming

“…[86] assessed the effect of maternal resveratrol intake of obese rats and found that resveratrol treatment restored adiponectin, AKT phosphorylation, brain-derived neurotrophic factor (BDNF) in male fetal brain; increased blood pressure, reduced increased body weight, peripheral insulin resistance in adult male offspring, further demonstrating that the intervention with this polyphenol may protects offspring against HFD-induced obesity. Another study using HFD-obese rats model [87] highlighted that the maternal resveratrol supplementation has a reprogramming role for progeny through lipid metabolic modulation. The authors showed that resveratrol treatment decreased lipogenesis and SIRT1 protein expression, attenuated leptin resistance, and increased lipolysis for progeny, resulting in an anti-obesity effect.…”