Maternal obesity increases insulin resistance, low-grade inflammation and osteochondrosis lesions in foals and yearlings until 18 months of age

Abstract

Introduction: Obesity is a growing concern in horses. The effects of maternal obesity on maternal metabolism and low-grade inflammation during pregnancy, as well as offspring growth, metabolism, low-grade inflammation, testicular maturation and osteochondrotic lesions until 18 months of age were investigated.

Material and methods: Twenty-four mares were used and separated into two groups at insemination according to body condition score (BCS): Normal (N, n = 10, BCS ≤4) and Obese (O, n = 14, BCS ≥4.25). BCS and plasma glucose, insulin, triglyceride, urea, non-esterified fatty acid, serum amyloid A (SAA), leptin and adiponectin concentrations were monitored throughout gestation. At 300 days of gestation, a Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) was performed. After parturition, foals' weight and size were monitored until 18 months of age with plasma SAA, leptin, adiponectin, triiodothyronine (T3), thyroxine (T4) and cortisol concentrations measured at regular intervals. At 6, 12 and 18 months of age, FSIGT and osteoarticular examinations were performed. Males were gelded at one year and expression of genes involved in testicular maturation analysed by RT-qPCR.

Results: Throughout the experiment, maternal BCS was higher in O versus N mares. During gestation, plasma urea and adiponectin were decreased and SAA and leptin increased in O versus N mares. O mares were also more insulin resistant than N mares with a higher glucose effectiveness. Postnatally, there was no difference in offspring growth between groups. Nevertheless, plasma SAA concentrations were increased in O versus N foals until 6 months, with O foals being consistently more insulin resistant with a higher glucose effectiveness. At 12 months of age, O foals were significantly more affected by osteochondrosis than N foals. All other parameters were not different between groups.

Conclusion: In conclusion, maternal obesity altered metabolism and increased low-grade inflammation in both dams and foals. The risk of developing osteochondrosis at 12 months of age was also higher in foals born to obese dams.

Fig 1. Experimental design.

(A)The year before insemination, the body condition score of barren mares was monitored. Normal (N, n = 10) mares had a fluctuant body condition score relevant to the nutrient availability whereas Obese (O, n = 14) mares had a high and stable body condition during the year. (B)From insemination until 6 months of gestation, pregnant mares were pastured as one same herd in the same pasture. From the 6th month of gestation, they were housed in individual boxes and fed the same amount of energy, proteins, fibre, calcium and phosphorus according to body weight until foaling. (C)From 3 days until 6 months of age, foals were kept in pasture with their dam. They were weaned by abrupt separation at 6 months, housed in open barns and fed the same amount of feed, following the French recommendations for growing foals [49]. Colts were castrated at 12 months as a routine procedure. From 12 to 18 months of age, all yearlings pastured in the same pasture. A.I.: Artificial insemination, BCS: body condition score.

Fig 2. Daily nutritional information (median and IQR) of feed distributed to Normal (N) and Obese (O) broodmares from wintering at 180 days of gestation until foaling.

There are no significant differences between groups. Net energy (A), horse digestible crude proteins (B), raw cellulose (C), and calcium to phosphorus ratio (D). BW: bodyweight.

Fig 3

Bodyweight (A) and body condition score (B) of mares (median and IQR) throughout pregnancy and lactation. For each time point, asterisks indicate a significant difference (p<0.05).

Fig 4

Basal plasma glucose (A) and insulin (B) concentration in pregnant Normal (n = 10) and Obese (n = 14) mares between 180 and 300 days of gestation.

Fig 5

Plasma triglycerides (A), non-esterified fatty acid (B), urea (C) and Serum amyloid A (D) concentration in pregnant Normal (n = 10) and Obese (n = 14) mares between 30 and 300 days of gestation or foaling. For each time point, asterisks indicate a significant difference between groups (p<0.05).

Fig 6

Plasma leptin (A) and adiponectin (B) concentrations in pregnant Normal (n = 10) and Obese (n = 14) mares from 180 days of gestation to foaling and correlations between insulin sensitivity calculated using the Bergman’s minimal model and plasma leptin concentrations (C) or plasma adiponectin concentrations (D) at 300 days of gestation. For each time point, asterisks indicate a significant difference between groups (p<0.05) and “T” indicate a tendency for a difference between groups (p<0.10).

Fig 7

Body weight (A), wither’s height (B), chest width (C) and body condition score (D) in Normal (n = 10) and Obese (n = 14) growing foals and yearlings. There was no difference between groups.

Fig 8. Plasma Serum amyloid A concentrations in Normal (n = 10) and Obese (n = 14) foals and yearling from birth to 12 months of age.

For each time point, asterisks indicate a significant difference between groups (p<0.05).

Fig 9

Serum cortisol (A), plasma leptin (B), adiponectin (C), T3 (D) and T4 (E) concentrations in Normal (n = 10) and Obese (n = 14) foals and yearling between birth and 12 or 18 months of age. For each time point, asterisks indicate a significant difference between groups (p<0.05).