Maternal High-Fat Diet Programs White and Brown Adipose Tissues In Vivo in Mice, with Different Metabolic and Microbiota Patterns in Obesity-Susceptible or Obesity-Resistant Offspring

Abstract

Maternal obesity causes metabolic dysfunction in the offspring, including dysbiosis, overeating, obesity, and type 2 diabetes. Early-life phases are fundamental for developing subcutaneous (SAT) and brown adipose tissues (BAT), handling energy excesses. Imaging of 18F-fluorodeoxyglucose by positron emission tomography (PET) and radiodensity by computerized tomography (CT) allows assessing adipose tissue (AT) whitening and browning in vivo and the underlying metabolic efficiency. Our aim was to examine these in vivo traits in SAT and BAT concerning gut microbiota composition in 1- and 6-month-old mice born to normal (NDoff) and high-fat diet-fed dams (HFDoff), accounting for body weight responses. We found low radiodensity (high lipids) in HFDoff SAT at 1 month, relating to an increased abundance of Dorea genus in the caecum and activation of the fatty acid biosynthetic pathway. Instead, low BAT radiodensity and glucose uptake were seen in adult HFDoff. Glucose was shifted in favor of BAT at 1 month and SAT at 6 months. In adults, unclassified Enterococcaceae and Rikenellaceae, and Bacillus genera were negatively related to BAT, whereas unclassified Clostridiales genera were related to SAT metabolism. Stratification of HFDoff based on weight-response, namely maternal induced obesity (MIO-HFDoff) or obesity-resistant (MIOR-HFDoff), showed sex dimorphism. Both subgroups were hyperphagic, but only obese mice had hyper-leptinemia and hyper-resistinemia, together with BAT dysfunction, whereas non-obese HFDoff had hyperglycemia and SAT hypermetabolism. In the caecum, unclassified Rikenellaceae (10-fold enrichment in MIO-HFDoff) and Clostridiales genera (4-fold deficiency in MIOR-HFDoff) were important discriminators of these two phenotypes. In conclusion, SAT whitening is an early abnormality in the offspring of HFD dams. In adult life, maternal HFD and the induced excessive food intake translates into a dimorphic phenotype involving SAT, BAT, and microbiota distinctively, reflecting maternal diet*sex interaction. This helps explain inter-individual variability in fetal programming and the higher rates of type 2 diabetes observed in adult women born to obese mothers, supporting personalized risk assessment, prevention, and treatment.

Maternal Brown Rice Diet during Pregnancy Promotes Adipose Tissue Browning in Offspring via Reprogramming PKA Signaling and DNA Methylation

“…[49] It has been found that high fat diet/high sugar diet/low protein diet during pregnancy reprogrammed the thermogenic function of the offspring by epigenetic reprogramming. [49][50][51][52] Maternal exposed to excess energy intake during pregnancy and lactation resulted in long-term impaired thermogenic ability and fatty acid oxidation in brown adipose tissue in offspring with the DNA hypermethylation of BATspecific genes involved in thermogenesis. [53] Adipose tissue browning and non-shivering thermogenesis are mainly controlled by 𝛽-adrenergic receptor (𝛽-AR) signaling pathways.…”

Programming Mechanism of Adipose Tissue Expansion in the Rat Offspring of Obese Mothers Occurs in a Sex-Specific Manner

“…Specifically, maternal obesity leads to excessive adipose tissue accumulation in the offspring. We [ 2 , 3 , 4 ] and others [ 5 , 6 , 7 ] demonstrated that maternal obesity programs their offspring to gender-specific metabolic alterations. The expansion pattern of white adipose tissue (WAT) is strongly linked to a greater possibility of developing metabolic alterations.…”