Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

Abstract

The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

Figure 1. Glucose (A), insulin (B), and leptin (C) levels for Control group (CONT), monosodium glutamate (MSG)-induced obese rats (F1), obese offspring (F2), and grand offspring (F3). Data are reported as means±SD (n=14 per group). *P<0.05 compared with CONT, ^#P<0.05 compared with F1, and ^&P<0.05 compared with F2 (ANOVA followed by Tukey's post hoc).

Figure 2. Gastrointestinal transit parameters evaluated for the Control group (CONT), monosodium glutamate (MSG)-induced obese rats (F1), obese offspring (F2), and grand offspring (F3). Mean gastric emptying time (MGET, A), mean cecum arrival time (B); mean small intestine transit time (C). Data are reported as means±SD (n=14 per group). *P<0.05 compared with CONT, ^#P<0.05 compared with F1, and ^&P<0.05 compared with F2 (ANOVA followed by Tukey's post hoc).

Figure 3. Gastric contractility parameters calculated for the Control group (CONT), monosodium glutamate (MSG)-induced obese rats (F1), obese offspring (F2), and grand offspring (F3). Frequency in contractions per min (cpm) (A) and amplitude (B) of gastric contractions. Data are reported as means±SD (n=14 per group). *P<0.05 compared with CONT, ^#P<0.05 compared with F1 (ANOVA followed by Tukey's post hoc).

Figure 4. Histological photomicrographs of H&E staining of the duodenum (A-D) of Control (CONT), monosodium glutamate (MSG)-induced obese rats (F1), obese offspring (F2), and grand offspring (F3) (×10 objective, scale bar, 50 μm). Quantification of the thickness of the duodenal circular muscle layer (E) and longitudinal muscle layer (F), crypt depth, villus height (G), and villus height to crypt depth ratio (H). Data are reported as means±SD (n=14 per group). *P<0.05 compared with CONT, ^#P<0.05 compared with F1, and ^&P<0.05 compared with F2 (ANOVA followed by Tukey's post hoc).