Maternal resistance to diet-induced obesity partially protects newborn and post-weaning male mice offspring from metabolic disturbances

Abstract

The rising rate of childhood overweight follows the increase in maternal obesity, since perinatal events impact offspring in a diversity of metabolic disorders. Despite many studies that have linked dietary consumption, overnutrition, or maternal obesity as the mediators of fetal metabolic programming, there are gaps regarding the knowledge about the contribution of different maternal phenotypes to the development of metabolic disturbances in offspring. This study aimed to investigate whether maternal high-fat diet (HFD) consumption without the development of the obese phenotype would protect offspring from metabolic disturbances. Female mice were fed standard chow diet or a HFD for 4 weeks before mating. HFD females were classified into obesity-resistant (OR) or obesity-prone (OP), according to weight gain. OP females presented with higher adiposity, fasting serum glucose and insulin, cholesterol and non-esterified fatty acid (NEFA). Newborn offspring from OP dams showed higher serum glucose and insulin and alteration in hepatic gene expression that may have contributed to the rise in hepatic fat content and decline of glycogen levels in the liver. Despite offspring from OR and OP females having showed similar growth after the day of delivery, offspring from OP females had higher caloric intake, fasting glucose, serum triglycerides and altered hepatic gene expression, as well as glucose and pyruvate intolerance and lower insulin sensitivity at d28 compared with offspring from OR females. Maternal pre-pregnancy serum glucose, insulin, and NEFA positively correlated with serum glucose and fat liver content and negatively correlated with hepatic glycogen in offspring. In conclusion, our results show that maternal resistance to diet-induced obesity partially protects offspring from early metabolic disturbances.

Low‐Dose Coconut Oil Supplementation Induces Hypothalamic Inflammation, Behavioral Dysfunction, and Metabolic Damage in Healthy Mice

“…Blood samples were obtained from the cut tip of tails and were used to determine glucose levels at 0, 5, 10, 15, 20 min. [ 26 ] In order to calculate insulin response, we analyzed the area under the curve (AUC).…”

Sex-Dependent Variations in Hypothalamic Fatty Acid Profile and Neuropeptides in Offspring Exposed to Maternal Obesity and High-Fat Diet

“…At mating, female mice fed a HF diet were obese, as evident by increased body weight and adiposity, higher energy intake, and elevated glycemia levels. It is widely established that the offspring of HF dams exhibit rapid body weight gain and increased adiposity, partly due to increased energy intake [6,14,23,43,44], suggesting a potential impairment in the development of neuronal circuits responsible for regulating energy homeostasis. Although the mechanisms have not been fully elucidated, the significance of long-chain polyunsaturated fatty acids (LC-PUFAs) in neuronal development has been the subject of investigation [45].…”

“…A Brazilian cohort study conducted in 2015 revealed that 47% of women were classified as overweight or obese before pregnancy [4]. In addition, obesity in children and adolescents (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years old) has increased significantly. In 1975, the global prevalence of obesity was 0.7% among girls and 0.9% among boys.…”

“…Numerous studies have demonstrated that the consumption of a hyperlipidemic or hypercaloric diet, as well as maternal obesity, is strongly linked to negative outcomes in offspring. These outcomes include impaired glucose metabolism and liver function, hyperactivity, cardiovascular disease, and obesity [7][8][9][10][11][12][13][14]. Maternal obesity can affect weight gain in offspring through various mechanisms, including its impact on hyperphagic mechanisms [15,16].…”

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

“…Recently, Simino et al proposed that let-7a was upregulated in livers at the delivery day and decreased the levels of AMP-activated protein kinase α2 (AMPKα2) protein and Lin28a, causing the metabolic disturbances of offspring from obesity-prone HFD-fed dams (OP-O) ( 26 ). They previously reported that OP-O mice presented higher hepatic TG, serum glucose/insulin and cholesterol levels, diminished Prkaa2 (the gene that encodes AMPKα2) and upregulated Fasn and Srebf1 (sterol regulatory element binding transcription factor 1) after weaning ( 134 ). This indicated that OP-O mice were early prone to developing metabolic disturbances, such as NAFLD.…”