Maternal High-Sucrose Diet Affects Phenotype Outcome in Adult Male Offspring: Role of Zbtb16

Abstract

Overnutrition in pregnancy and lactation affects fetal and early postnatal development, which can result in metabolic disorders in adulthood. We tested a hypothesis that variation of the Zbtb16 gene, a significant energy metabolism regulator, modulates the effect of maternal high-sucrose diet (HSD) on metabolic and transcriptomic profiles of the offspring. We used the spontaneously hypertensive rat (SHR) strain and a minimal congenic rat strain SHR- Zbtb16 , carrying the Zbtb16 gene allele originating from the PD/Cub rat, a metabolic syndrome model. Sixteen-week-old SHR and SHR- Zbtb16 rat dams were fed either standard diet (control groups) or a high-sucrose diet (HSD, 70% calories as sucrose) during pregnancy and 4 weeks of lactation. In dams of both strains, we observed an HSD-induced increase of cholesterol and triacylglycerol concentrations in VLDL particles and a decrease of cholesterol and triacylglycerols content in medium to very small LDL particles. In male offspring, exposure to maternal HSD substantially increased brown fat weight in both strains, decreased triglycerides in LDL particles, and impaired glucose tolerance exclusively in SHR. The transcriptome assessment revealed networks of transcripts reflecting the shifts induced by maternal HSD with major nodes including mir-126, Hsd11b1 in the brown adipose tissue, Pcsk9, Nr0b2 in the liver and Hsd11b1, Slc2a4 in white adipose tissue. In summary, maternal HSD feeding during pregnancy and lactation affected brown fat deposition and lipid metabolism in adult male offspring and induced major transcriptome shifts in liver, white, and brown adipose tissues. The Zbtb16 variation present in the SHR- Zbtb16 led to several strain-specific effects of the maternal HSD, particularly the transcriptomic profile shifts of the adult male offspring.

Energy Metabolism and Lipidome Are Highly Regulated during Osteogenic Differentiation of Dental Follicle Cells

“…This is very interesting with regard to the previous observation that dexamethasone-induced mineralization is more intense compared to BMP2-treated DFCs [ 13 ]. The transcription factor ZBTB16, whose expression is highly induced by dexamethasone [ 11 ], might play a role for this difference as it is also related to energy metabolism [ 51 ]. A study on rabbit MSCs could further show that the lipidome changes during osteogenic differentiation of precursor cells and, moreover, that lipidomes are similar in cells from different origins [ 52 ].…”

Ventromedial hypothalamic nucleus subset stimulates tissue thermogenesis via preoptic area outputs

“…S6B ): Zbtb16 and Slc26a8 are also found to be involved in induction of mitochondrial metabolism and uncoupling capacity. Zbtb16 is a significant energy metabolism modulator and overexpression of the gene has been found to induce thermogenic programming including induction of mitochondrial fatty acid oxidation and uncoupling/electron transport chain [ 50 , 51 ]. The Slc26a8 gene is known to stimulate anion transport activity of the cystic fibrosis transmembrane conductance regulator (CFTR) which in turn facilitates ATP synthesis, ATP transport, and influences energy expenditure by regulating nutrient absorption and digestion [ 52 , 53 ].…”

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

“…de Almeida-Faria et al ( 106 ) also found that feeding an obesogenic diet after weaning resulted in increased IRS-1 degradation, which suggests that exposure to obese individuals in utero combined with a postweaning obesogenic diet could significantly increase the risk of T2D. Moreover, the expression of miR-126 also changed in brown fat deposition and lipid metabolism of adult male offspring exposed to maternal high-sucrose diet ( 107 ). The reasons for this was unclear, but probably due to variation in the Zbtb16 gene ( 107 ).…”

“…Moreover, the expression of miR-126 also changed in brown fat deposition and lipid metabolism of adult male offspring exposed to maternal high-sucrose diet ( 107 ). The reasons for this was unclear, but probably due to variation in the Zbtb16 gene ( 107 ).…”