Maternal Insulin Resistance during Late Gestation Impairs Brown Adipose Tissue Development and Thermogenic Function in Calves

This study investigated the impact of maternal insulin resistance (IR) during late gestation on brown adipose tissue (BAT) development and thermogenic function in neonatal calves. Forty-four dry Holstein cows were selected for the study. Blood samples were collected during the dry period to assess insulin and glucose concentrations, and maternal IR was evaluated using the Homeostasis Model Assessment (HOMA-IR). The cows were divided into 2 groups: maternal-low-IR (n = 22) and maternal-high-IR (n = 22). Immediately after birth, calves were separated from their dams and closely monitored for growth. Calf health was monitored from birth to one month of age, 3 times per week, using standardized clinical scoring of fecal consistency, cough, nasal discharge, and respiration rate. Body weight, body length, withers height, and rectal temperature were recorded at birth, and blood glucose levels were assessed at various intervals following a glucose tolerance test (GTT). At birth (n = 10 per group) and at one month (n = 12 per group), calves were euthanized, and perirenal BAT samples were collected for histological and molecular analyses. Thermogenic and mitochondrial dynamics markers were evaluated at the mRNA and protein levels using quantitative PCR and Western blotting. Stromal vascular fractions (SVFs) from perirenal BAT collected from calves at 0 d of age were cultured under hyperglycemic and hyperinsulinemic conditions to assess their differentiation into brown adipocytes, lipid droplet formation, and gene expression of key thermogenic markers, including UCP1 and dynamin-related protein 1 (DRP1). The results showed that maternal IR significantly increased serum insulin and glucose levels in cows but did not affect body condition score (BCS) or backfat thickness (BFT). At birth, calves from high-IR dams had significantly lower perirenal BAT mass and larger brown adipocytes. Gene expression of thermogenic markers, such as UCP1 and PGC-1α, was downregulated, and mitochondrial density in BAT was significantly reduced in maternal-high-IR calves. These effects persisted at one month, with continued reductions in BAT mass, mitochondrial density, and thermogenic gene expression. maternal-high-IR calves exhibited impaired glucose tolerance, with delayed glucose clearance in the GTT. Maternal-high-IR calves also showed increased clinical morbidity, including higher fecal scores, increased cough scores, and a greater incidence of diarrhea. In vitro, SVFs from calves demonstrated significantly reduced lipid droplet formation and impaired thermogenic gene expression. Mitochondrial fission markers DRP1 and FIS1 were downregulated in the maternal-high-IR group. These results suggest that maternal IR during late gestation impairs BAT development, mitochondrial dynamics, and glucose metabolism in neonatal calves, leading to long-term consequences for thermogenic function and metabolic health.