Chronic stress and high sucrose intake cause distinctive morphometric effects in the adrenal glands of post-weaned rats.

We investigated the effects of chronic stress combined with high sucrose intake on the morphology of the adrenal glands in young rats. Male Wistar rats were fed a standard chow diet and allocated into control (C; tap water), chronic restraint stress (St), 30% sucrose diet (S30) and 30% sucrose diet + chronic restraint stress (S30 + St) groups. St consisted of 1 h daily sessions, 5 days/week for 4 weeks. Chronic stress reduced the thickness of the zona glomerulosa (ZG) and zona fasciculata (ZF) in both right and left glands; the thickness of the zona reticularis (ZR) was increased in the right gland. Cell density was greater in the ZF and medulla of both right and left glands, whereas cell density increased in the ZR of only the left gland. The percentage of small cells was lower in the ZG, whereas more large cells were found in the left gland. A similar result was obtained for the ZF, ZR and medulla in both right and left glands. Chronic stress increased the area covered by blood vessels in the ZR of the right gland, but decreased the area in the ZR of the left gland. The area covered by blood vessels was reduced in the medulla of both right and left glands in rats subjected to chronic stress. Infiltration of immune cells was increased by chronic stress in all layers of the cortex of the left gland, but was reduced in the medulla of the right gland. A high sucrose diet reduced the thickness of the medulla in the left gland. Cell proliferation increased in the ZG of the right gland and the weight of the right adrenal gland increased. Reduced cell proliferation in the ZG of the left gland was associated with a reduction in the area covered by blood vessels. In addition, the area covered by blood vessels decreased in the medulla of both glands. Our findings demonstrate that exposure to chronic stress during early life causes morphometric changes in adrenal glands.

Hitting a triple in the non-alcoholic fatty liver disease field: sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed a gestational low-protein diet.

The excessive consumption of carbohydrates is related to non-alcoholic fatty liver disease (NAFLD) in infants and adults. The effect of combining maternal malnutrition and a high carbohydrate intake on the development of NAFLD in adulthood remains unknown. We therefore hypothesized that consumption of 5% sucrose by the offspring of dams fed a low-protein diet during pregnancy promotes liver fat accumulation and oxidative damage differently in females and males. To test this, 12-month-old female and male offspring of mothers fed a Control (C) or low-protein diet (Restricted, R) were provided with either tap water or 5% sucrose for a period of 10 weeks. Livers were excised to measure the fat content and 3-nitrotyrosine (3-NTyr) immunostaining; serum samples were also obtained to measure the concentration of malondialdehyde (MDA). Data were analyzed using a non-repeated measures three-way analysis of variance to determine significant differences (P<0.05) regarding to the interaction among maternal diet, sucrose consumption and sex. Results showed that the liver fat content of females from R mothers was higher than that of their male counterpart. Hepatic 3-NTyr immunostaining and serum MDA concentrations were not affected by the interaction involving maternal diet, sucrose consumption and sex. Otherwise, liver fat content was correlated with the hepatic 3-NTyr immunostaining and serum MDA concentrations only in females. Thus, sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed with a low-protein diet during pregnancy. This research emphasizes the importance of a balanced diet during pregnancy and the influence of the diet on the adult offspring.

Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor.

Hypothyroidism is associated with the development of non-alcoholic steatohepatitis, but cellular mechanisms have been scarcely analyzed. Thyroid hormones regulate the synthesis and secretion of bile acids that are endogenous ligands of the farnesoid receptor (FXRα), which have been involved in the development of non-alcoholic steatohepatitis. However, the relationship between thyroid hormones and FXRα expression in the liver is yet unknown. Control (n=6) and methimazole-induced hypothyroid (n=6) female rabbits were used to evaluate the amount of lipids and glycogen, vascularization, hepatocytes proliferation, immune cells infiltration, and expression of FXRα. Student-t or Mann-Whitney U tests were carried out to determine significant differences. Hypothyroidism induced steatosis, glycogen loss, fibrosis, and a minor vascularization in the liver. In contrast, hypothyroidism increased the proliferation of hepatocytes and the infiltration of mast cells, but did not modify the number of immune cells into sinusoids. These changes were associated with a minor anti-FXRα immunoreactivity of periportal hepatocytes and pericentral immune cells. Our results suggest that hypothyroidism induces a moderate non-alcoholic steatohepatitis, alllowing the hepatic regeneration. The FXRα may be involved in the development of non-alcoholic steatohepatitis in hypothyroid subjects.

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits.

Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.