Subacute cadmium exposure changes different metabolic functions, leading to type 1 and 2 diabetes mellitus features in female rats.

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd-exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd-exposed rats had increased liver cholesterol levels, insulin receptor beta (IRß) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.

Single microcystin exposure impairs the hypothalamic-pituitary-gonadal axis at different levels in female rats.

Microcystin (MC) is most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis and metabolic function. In this study, we assessed whether MC exposure results in HPG axis and metabolic changes. Female rats were exposed to a single dose of MC at environmentally relevant levels (5, 20 and 40 µg/kg). After 24 h, we evaluated reproductive and metabolic parameters for 15 days. MC reduced the hypothalamic GnRH protein expression, increased the pituitary protein expression of GnRHr and IL-6. MC reduced LH levels and increased FSH levels. MC reduced the primary follicles, increased the corpora lutea, elevated levels of anti-Müllerian hormone (AMH) and progesterone, and decreased estrogen levels. MC increased ovarian VEGFr, LHr, AMH, ED1, IL-6 and Gp91-phox protein expression. MC increased uterine area and reduced endometrial gland number. A blunted estrogen-negative feedback was observed in MC rats after ovariectomy, with no changes in LH levels compared to intact MC rats. Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.

Effects of microcystin-LR on mammalian ovaries.

The ovaries play critical roles in regulating oocyte maturation and sex steroid hormone production and thus are critical for female reproduction. Ovarian function relies on hormone receptors and signaling pathways, making the ovaries potential targets for environmental factors, such as microcystins (MCs). MCs are a diverse group of cyanobacterial toxins generally found in eutrophic water or algal blooms. Here, we review relevant research on the associations between MC exposure and ovarian dysfunction, including their effects on ovarian morphology, folliculogenesis, steroid production, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, and fertility. This review covers the most recent in vitro and in vivo studies in mammals. We also discuss important gaps in the literature. Overall, current evidence indicates that MC exposure causes impairments in ovarian function, but further studies are needed to elucidate the mechanisms through which MCs affect ovarian function and other female endocrine functions.

Subacute and low dose of tributyltin exposure leads to brown adipose abnormalities in male rats.

Tributyltin (TBT) is an obesogenic endocrine disrupting chemical (EDC) linked with several metabolic complications. Brown adipose tissue (BAT) is the principal site for thermogenesis, making it a potential target for obesity management and metabolic disease. However, few studies have evaluated TBT effect on BAT function. In this investigation, we assessed whether subacute (15 days) and low dose of TBT exposure (100 ng/kg/day) results in abnormal BAT morphophysiology in adult male rats. Body temperature, BAT morphology, inflammation, oxidative stress, collagen deposition and BAT metabolic gene expression markers were assessed in room temperature (Room, ∼24 ºC) and after cold tolerance test (Cold, ∼4 ºC) conditions. A reduction in body temperature was observed in both Room and Cold conditions in TBT rats, suggesting abnormal BAT thermogenic function. Changes in BAT morphology were observed in TBT rats, with an increase in BAT lipid accumulation, an increase in BAT unilocular adipocyte number and a decrease in BAT multilocular adipocyte number in Room condition. All these parameters were opposite in Cold condition TBT rats, leading to a borderline increase in BAT UCP1 protein expression. An increase in BAT mast cell number was observed in TBT rats in Room condition. An increase in ED1 protein expression (macrophage marker) was observed in TBT rats in Cold condition. Oxidative stress and collagen deposition increased in both Room and Cold conditions in TBT rats. TBT exposure caused a borderline increase in BAT COL1A1 protein expression in Cold condition. Further, strong negative correlations were observed between body temperature and BAT lipid accumulation, and BAT lipid accumulation and multilocular adipocyte number. Thus, these data suggest that TBT exposure impaired BAT morphophysiology through impacts on lipid accumulation, inflammation, fibrosis and oxidative stress in male rats.

High-refined carbohydrate diet alters different metabolic functions in female rats.

A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.