Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells.

ABSTRACT

BACKGROUND: The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated. AIM: To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring. METHODS: Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. Bone MSCs (BMSCs) were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/ß-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk, along with normal-fat diet as the control. Then the serum was collected for the measurement of biochemical indicators. Meanwhile, the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration. And the target gene expressions on the adipogenic differentiation and Wnt/ß-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction. RESULTS: Compared with the control group, maternal deficient, low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity, with larger adipocytes, more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation (PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and/or Leptin) among their male offspring (P < 0.05). And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro, respectively (P < 0.05). Meanwhile, it was accompanied by more significant disorders on the expressions of Wnt/ß-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups. CONCLUSION: Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring, with significant expressions on the Wnt/ß-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.