Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet.

SCOPE: Perinatal maternal moderately high-fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n-3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning. METHODS AND RESULTS: Female Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high-fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics. CONCLUSIONS: Gestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long-term outcomes.

Cinnamaldehyde treatment during adolescence improves white and brown adipose tissue metabolism in a male rat model of early obesity.

Early obesity is a serious health problem and nutritional therapeutic strategies during young age may improve health outcomes throughout life. Cinnamaldehyde, the major component of cinnamon, exhibits several beneficial metabolic effects. Here we tested the impact of cinnamaldehyde treatment during adolescence in a rat model of obesity programmed by early overnutrition, addressing white (WAT) and brown adipose tissue (BAT). After birth, litters were adjusted to 10 pups or 3 pups (small litter) to induce overfeeding and early obesity. On postnatal day 30, half of the small litter pups received cinnamaldehyde (40 mg per kg of body mass per day) for 30 days. The animals were studied at the end of the treatment at 60 days of age and 4 months thereafter (180 days old). The early overfeeding programmed to higher epididymal WAT mass, adipocyte hypertrophy at both ages, and higher BAT mass associated with higher lipid accumulation in the long term. Cinnamaldehyde reduced the adipocyte hypertrophy associated with reduced lipogenesis machinery expression (Srebf1c, Acaca), while it stimulated oxidative ones (Ppargc1a, Fgf21) in WAT, and increased BAT thermogenesis markers (Ppara, Fgf21, Ucp1). In the long term, cinnamaldehyde treatment reprogrammed the metabolism leading to a diminished WAT adipocyte size, accompanied by reduced expression of lipogenesis-related genes (Pparg, Dgat2). In BAT, cinnamaldehyde led to reduced lipogenesis marker expression (Pparg, Lpl) associated with the reduced whitening phenotype, and a robust increase in Fgf21 expression. These results suggest that cinnamaldehyde intake during adolescence has long-lasting benefits in WAT and BAT metabolism, reinforcing its potential as a reprogramming nutraceutical in the treatment of childhood obesity.

Treatment with cinnamaldehyde reduces the visceral adiposity and regulates lipid metabolism, autophagy and endoplasmic reticulum stress in the liver of a rat model of early obesity.

Nutrition at early stages of life contributes to the alarming incidence of childhood obesity, insulin resistance and hepatoesteatosis. Cinnamaldehyde, major component of cinnamon, increases insulin sensitivity and modulates adiposity and lipid metabolism. The aim of this study was to analyze the impact of cinnamaldehyde treatment during adolescence in a rat model of early obesity. Litter size reduction was used to induce overfeeding and early obesity. At postnatal day 30 (adolescence), the male Wistar rats received cinnamaldehyde by gavage (40 mg/kg of body weight/day) for 29 days and were studied at the end of treatment at 60 days old or 4 months thereafter (180 days old). At 60 days of age, the treatment with cinnamaldehyde promoted reduced visceral adiposity, serum triacylglycerol, and attenuation of energy efficiency and insulin resistance. In the liver, it reduced lipid synthesis, stimulated autophagy and reduced ER stress. At 180 days of age, animals treated with cinnamaldehyde during the adolescence exhibited normalization of visceral adiposity and energy efficiency, and attenuation of hyperphagia, serum hypertriglyceridemia and hepatic triacylglycerol content, with molecular markers indicative of reduced hepatic synthesis. However, the beneficial effect observed at 60 days of age on glucose homeostasis, autophagy and ER stress was lost. Therefore, the cinnamaldehyde supplementation during the adolescence has short- and long-term metabolic beneficial effects, highlighting its potential as an adjuvant in the treatment of early obesity.

Maternal cinnamon intake during lactation led to visceral obesity and hepatic metabolic dysfunction in the adult male offspring.

PURPOSE: Studies with foods, known to promote health benefits in addition to the nutritive value, show that their consumption by pregnant and/or lactating females could induce negative outcomes to the offspring. It is well characterized that cinnamon intake promotes benefits to energy homeostasis. The present study aimed to analyze the effects of the consumption of an aqueous extract of cinnamon by lactating female rats on the endocrine-metabolic outcomes in the adult offspring. METHODS: Lactating dams (Wistar rats) were supplemented with cinnamon aqueous extract (400 mg/kg body weight/day) for the entire lactating period. The male adult offspring were evaluated at 180 days old (CinLac). RESULTS: The offspring presented visceral obesity (P = 0.001), hyperleptinemia (P = 0.002), and hyperinsulinemia (P = 0.016). In the liver, CinLac exhibited reduced p-IRß (P = 0.018) suggesting insulin resistance. However, phosphorylation of IRS1 (P = 0.041) and AKT (P = 0.050) were increased. JAK2 (P = 0.030) and p-STAT3 (P = 0.015) expressions were higher, suggesting that the activation of IRS1/AKT in the CinLac group could have resulted from the increased activation of leptin signaling. Although we observed no changes in the gluconeogenic pathway, the CinLac group exhibited lower hepatic glycogen content (P = 0.005) accompanied by increased p-GSK3ß (P = 0.011). In addition, the CinLac group showed increased hepatic triacylglycerol content (P = 0.049) and a mild steatosis (P = 0.001), accompanied by reduced PPARα mRNA expression (P = 0.005). CONCLUSION: We conclude that maternal intake of aqueous extract of cinnamon induces long-term molecular, metabolic, and hormonal changes in the adult progeny, including visceral obesity, higher lipid accumulation, and lower glycogen content in the liver.