Pancreatic ultrastructural enhancement due to telmisartan plus sitagliptin treatment in diet-induced obese C57BL/6 mice.

OBJECTIVE: We sought to evaluate the effects of telmisartan, sitagliptin, or their combination on pancreatic ultrastructural alterations in high-fat-fed C57BL/6 mice. METHODS: Three-month-old C57BL/6 mice were fed with standard chow (SC, 10% lipids) or high-fat diet (HF, 60% lipids) during 10 weeks to induce obesity and its comorbidities. After this period, treatment began (lasted 6 weeks), and the HF group was divided into 4 subgroups: untreated HF, HF plus telmisartan (5 mg/kg per day), HF plus sitagliptin (1.1 g/kg per day), and HF plus telmisartan plus sitagliptin. Drugs were mixed with diet. Biochemical analyses, radioimmunoassay, immunofluorescence, stereology, and transmission electron microscopy were performed to assess pancreatic remodeling. RESULTS: Overweight, hyperinsulinemia, hyperglycemia, and dyslipidemia were found in the HF group, but these outcomes were controlled by the different treatments. Untreated HF animals also showed alterations concerning distribution of α/ß cell followed by large and numerous lipid droplets within pancreas. Telmisartan and sitagliptin as monotherapy alleviated these findings, and a complete reversal of pancreatic steatosis was observed after treating with the combination of the 2 drugs. CONCLUSIONS: AT1 receptor blockade, partial peroxisome proliferator-activated receptor gamma activation, and extended incretin action emerge as feasible strategies to control pancreatic steatosis and avoid progression of pancreatic diseases due to lipotoxicity.

Effects of maternal undernutrition during lactation on estrogen and androgen receptor expressions in rat ovary at puberty.

OBJECTIVE: The aim of this study was to evaluate the effects of maternal protein and energy-restricted diets during lactation in folliculogenesis and its relations to androgen and estrogen receptors in the offspring at puberty. METHODS: At parturition, dams were randomly assigned to a control (C) group, with free access to a standard laboratory diet containing 23% protein; a protein-energy-restricted (PER) group, with free access to an iso-energy and protein-restricted diet containing 8% protein; and an energy-restricted (ER) group, receiving standard laboratory diet in restricted quantities. After weaning, female pups had free access to standard laboratory diet. RESULTS: The number of preantral (C 13.72 ± 2.87, PER 26.36 ± 3.03, ER 26.88 ± 2.31, P < 0.05) and small antral (C 9.32 ± 1.32, PER 17.64 ± 2.33, ER 17.04 ± 2.22, P < 0.05) follicles was significantly increased by maternal malnutrition. The number of primordial follicles (C 10.57 ± 1.61, PER 4.30 ± 0.62, ER 6.28 ± 1.30, P < 0.05), Graafian follicles (C 1.04 ± 0.09, PER 0.52 ± 0.10, ER 0.36 ± 0.11, P < 0.01), and corpus luteum (C 4.84 ± 0.62, PER 2.80 ± 0.50, ER 3.24 ± 0.27, P < 0.05) was significantly reduced. Maternal protein- and energy-restricted diets led to a significant decrease in the androgen (C 9815 ± 1015, PER 6071 ± 838.7, ER 5811 ± 699.3, P < 0.05) and estrogen (C 0.79 ± 0.244, PER 0.12 ± 0.035, ER 0.20 ± 0.036, P < 0.05) α-receptors. In growing follicles, androgen receptor was immuno-expressed in granulosa and theca cells. Estrogen receptor-α was mainly expressed in stroma cells. CONCLUSION: Our results suggest that maternal protein- and energy-restricted diets during lactation can disturb the follicular development of the offspring, probably by reducing the number of androgen and estrogen receptors in the ovary.

Metabolic programming of ovarian angiogenesis and folliculogenesis by maternal malnutrition during lactation.

OBJECTIVE: To evaluate whether maternal malnutrition during lactation programs ovarian folliculogenesis and the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and its receptors KDR, Flt-1, and FGFR. DESIGN: Experimental study. SETTING: University-based research laboratory. ANIMAL(S): Adult female rats from a urogenital research laboratory. INTERVENTION(S): Six rat dams randomly assigned to the following groups: control group (C), with free access to a standard laboratory diet containing 23% protein; and a protein-energy-restricted group (PER), with free access to an isoenergy and protein-restricted diet containing 8% protein. After weaning, the female pups had free access to the standard laboratory diet until 90 days of age, when they were sacrificed at the proestrum stage. MAIN OUTCOME MEASURE(S): Quantification of ovarian follicles, vessels, and expression of growth factors and their receptors. RESULT(S): Maternal malnutrition during lactation caused a significant reduction in the number of primordial (C = 6.60 +/- 0.24, PER = 5.20 +/- 0.20), primary (C = 5.80 +/- 0.66, PER = 4.00 +/- 0.31), and Graafian follicles/section (C = 2.18 +/- 0.29, PER = 1.08 +/- 0.37), in KDR (C = 0.22 +/- 0.04, PER = 0.09 +/- 0.01), Flt-1 (C = 0.28 +/- 0.05, PER = 0.12 +/- 0.02), and FGFR mRNA expression (C = 0.34 +/- 0.05, PER = 0.13 +/- 0.05) and in the vessel density of follicles (C = 17.26 +/- 2.30, PER = 9.96 +/- 0.97). CONCLUSION(S): Maternal malnutrition during lactation programs the follicular development by a reduction of VEGF and FGF mRNA receptors expression, probably from a direct action on the follicular development or a reduction in vasculature resulting in a decreased delivery of folliculotrophic substances in PER animals.

Maternal malnutrition during lactation affects folliculogenesis, gonadotropins, and leptin receptors in adult rats.

OBJECTIVE: The goal of this study was to evaluate if maternal malnutrition during lactation could possibly program folliculogenesis, the ovarian expression of gonadotropins, leptin, and their receptors. METHODS: At parturition, dams were randomly assigned to a control group (C), with free access to a standard laboratory diet containing 23% protein, and a protein-energy-restricted group (PER), with free access to an iso-energy and protein-restricted diet containing 8% protein. After weaning, all female pups had free access to the standard laboratory diet until 90 d of age when they were euthanized in the diestrum stage. RESULTS: Maternal malnutrition caused decreases in the number of primordial (C 6.60 ± 0.24, PER 5.20 ± 0.20, P = 0.01), primary (C 5.80 ± 0.66, PER 4.00 ± 0.31, P = 0.04), and Graafian (C 2.18 ± 0.29, PER 1.08 ± 0.37, P = 0.05) follicle numbers. Maternal malnutrition led to a significant decrease in the aromatase mRNA expression (C 0.536 ± 0.008, PER 0.353 ± 0.041, P = 0.01) follicle-stimulating hormone receptor (C 1.25 ± 0.17, PER 0.75 ± 0.02, P = 0.04), luteinizing hormone receptor (C 0.93 ± 0.09, PER 0.54 ± 0.10, P = 0.03), leptin (C 0.55 ± 0.03, PER 0.42 ± 0.03, P = 0.04), Ob-R (C 1.05 ± 0.12, PER 0.64 ± 0.07, P = 0.03), and Ob-Rb (C 1.34 ± 0.21, PER 0.47 ± 0.10, P = 0.02) transcripts when compared with C. CONCLUSION: Maternal malnutrition during lactation modulates folliculogenesis and the expression of the different isoforms of leptin and gonadotropin receptors and the aromatase enzyme. This probably is a consequence of alterations in perinatal leptin concentrations that may play a crucial role in determining the occurrence of long-term metabolic changes.

Maternal protein-energy and energy-restricted diets during lactation possibly could program folliculogenesis and the ovarian expression of leptin and its different isoform receptors in rats.

Both protein-energy and energy-restricted diets during lactation program the ovarian function of the rat offspring, leading to a reduction of folliculogenesis, possibly as the consequence of the altered expression of leptin and its isoform receptor genes.

Morphological modification of female bladder after prolonged use of soy-based diets.

OBJECTIVES: The aim of this study was to compare the effects of a prolonged use of organic and transgenic soy upon the lipid profile and the collagen/muscle ratio of the detrusor muscle of the bladder. METHODS: Wistar rats were fed three different diets from weaning until sacrifice (15 months old): control group (CG) casein-based diet; organic soy group (OSG) organic soy-based diet; genetically modified soy group (GMSG) transgenic soy-based diet. RESULTS: There was no difference in the food consumption or in the diet isoflavone components among the groups. Comparing to CG, both OSG and GMSG groups presented a significant (p<0.05) reduction in the body weight, triglycerides, cholesterol and the smooth muscle of the detrusor and a significant (p<0.05) increase of collagen fibers number of the detrusor muscle. CONCLUSIONS: These findings call into question that, the prolonged use of soy-based diets can be deleterious to the bladder by altering the collagen/muscle ratio what can cause bladder dysfunctions similar with that occurring during menopause.

Puberty onset in the female offspring of rats submitted to protein or energy restricted diet during lactation.

This study aims to determine the effects of maternal protein and energy malnutrition during lactation on the linear growth, body weight and onset of puberty of the female offspring. At parturition, dams were randomly assigned to the following groups: (C) control group, with free access to a standard laboratory diet containing 23% protein; (PR) protein-restricted group, with free access to an isoenergy and protein-restricted diet containing 8% protein; and (ER) energy-restricted group, receiving standard laboratory diet in restricted quantities. After weaning, the female pups had free access to standard laboratory diet. From day 30 onwards, the pups were inspected daily for vaginal opening. Cyclic stages of the ovaries were studied by daily vaginal smears after vaginal opening until day 40 when all animals were sacrificed with pentobarbital. From day 4 after birth until day 40, body weight and linear growth in the PR and ER rats were significantly lower than in controls (p < 0.001). In spite of the significant (p<0.05) delayed in the vaginal opening in PR and ER rats, the first estrous cycle occurred at the same time of vaginal opening in all groups. The PR and ER rats exhibited a lower uterine (PR = 42%, ER = 40%, p < 0.001) and ovarian (PR = 26%, ER=19%, p < 0.05) absolute weight and uterus relative weight (PR = 27%, ER = 22%, p < 0.05). Our data showed that maternal protein and energy malnutrition during lactation leads to growth retardation and delayed on the onset of puberty in female pups, with vaginal opening and estrous cycle occurring at the same time.