P.0069 Prenatal N-acetyl-cysteine prevents social anxiety and modulates hippocampal inflammatory-and plasticity-related genes in adolescent mice prenatally exposed to a high-fat diet

Infants born to diabetic or obese mothers are at greater risk of heart disease at birth and throughout life, but prevention is hindered because underlying mechanisms remain poorly understood. Using a rat model, we showed that prenatal exposure to maternal diabetes and a high-fat diet caused diastolic and systolic dysfunction, myocardial lipid accumulation, decreased respiratory capacity, and oxidative stress in newborn offspring hearts. This study aimed to determine whether mitochondrial dynamism played a role. Using confocal live-cell imaging, we examined mitochondrial dynamics in neonatal rat cardiomyocytes (NRCM) from four prenatally exposed groups: controls, diabetes, high-fat diet, and combination exposed. Cardiac expression of dynamism-related genes and proteins were compared, and gender-specific differences were evaluated. Findings show that normal NRCM have highly dynamic mitochondria with a well-balanced number of fusion and fission events. Prenatal exposure to diabetes or a high-fat diet impaired dynamism resulting in shorter, wider mitochondria. Mechanisms of impaired dynamism were gender-specific and protein regulated. Females had higher expression of fusion proteins which may confer a cardioprotective effect. Prenatally exposed male hearts had post-translational modifications known to impair dynamism and influence mitophagy-mediated cell death. This study identifies mitochondrial fusion and fission proteins as targetable, pathogenic regulators of heart health in offspring exposed to excess circulating maternal fuels.

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N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function

Frontiers in Pharmacology ◽

10.3389/fphar.2021.636204 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weijian Hang ◽

Hongyang Shu ◽

Zheng Wen ◽

Jinyan Liu ◽

Zhiyuan Jin ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Mitochondrial Function ◽

High Fat Diet ◽

Fatty Liver Disease ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Triglyceride Accumulation ◽

Acetyl Cysteine

Rationale: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic disease characterized by liver steatosis. Excessive reactive oxygen species (ROS) originating from dysfunctional mitochondria is the major pathophysiological contributor in the development of NAFLD and is thought to be a promising therapeutic target. A few reports demonstrate the antioxidative treatments for NAFLD.Methods: Male C57 mice were fed on a normal chow diet (ND) or high-fat diet (HFD) for 8 weeks. PBS or N-acetyl cysteine (NAC) was gavaged to mice. LO2 human liver cell line treated with palmitic acid (PA) was applied as a cellular model. Western blot, immunofluorescence, biochemistry assay, and pathological staining were used to investigate the mechanism of suppressing lipid accumulation of NAC.Results: NAC treatment was able to prevent HFD-induced NAFLD, as evidenced by less hepatic triglyceride accumulation and lipid droplet formation compared with that of mice in the HFD group. NAC could preserve mitochondrial function by inhibiting excessive mitophagy and promoting mitochondria biogenesis to prevent ROS production. NAC also activated Sirt1 and preserved its protein level and subsequently promoted mitochondria biogenesis via deacetylating PGC1a.Conclusion: We demonstrated that NAC may be an effective drug to treat NAFLD, which was related to its antioxidative and mitochondrial protective effect.

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Abstract # P-20: 11b-Hydroxysteroid Dehydrogenase 1 Regulation in High Fat Diet Induced Insulin Resistant Rats and Rats Treated with Sutherlandia Frutescens

Endocrine Practice ◽

10.1016/s1530-891x(20)43833-9 ◽

2016 ◽

Vol 22 ◽

pp. 23

Author(s):

Ngozi F. Nnolum-Orji ◽

Saartjie Roux ◽

Janine Mackenzie ◽

Disang Lekutlane

Keyword(s):

High Fat Diet ◽

Hydroxysteroid Dehydrogenase ◽

High Fat ◽

Insulin Resistant ◽

Sutherlandia Frutescens

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Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000259 ◽

2019 ◽

Vol 89 (1-2) ◽

pp. 45-54

Author(s):

Akemi Suzuki ◽

André Manoel Correia-Santos ◽

Gabriela Câmara Vicente ◽

Luiz Guillermo Coca Velarde ◽

Gilson Teles Boaventura

Keyword(s):

Thyroid Hormones ◽

High Fat Diet ◽

Female Offspring ◽

Flaxseed Oil ◽

Diabetic Rats ◽

High Fat ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Flaxseed Flour ◽

Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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