Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen exposure during intrauterine life in nonhuman primates and in sheep results in a phenocopy of the reproductive and metabolic features of polycystic ovary syndrome (PCOS). Such exposure also results in reproductive features of PCOS in rodents. We investigated whether transient prenatal androgen treatment produced metabolic abnormalities in adult female rats and the mechanisms of these changes. Pregnant dams received free testosterone or vehicle injections during late gestation, and their female offspring were fed regular or high-fat diet (HFD). At 60 days of age, prenatally androgenized (PA) rats exhibited significantly increased body weight; parametrial and subcutaneous fat; serum insulin, cholesterol and triglyceride levels; and hepatic triglyceride content (all P < 0.0125). There were no significant differences in insulin sensitivity by intraperitoneal insulin tolerance test or insulin signaling in liver or skeletal muscle. HFD had similar effects to PA on body weight and composition as well as on circulating triglyceride levels. HFD further increased hepatic triglyceride content to a similar extent in both PA and control rats. In PA rats, HFD did not further increase circulating insulin, triglyceride, or cholesterol levels. In control rats, HFD increased insulin levels, but to a lesser extent than PA alone ( approximately 2.5- vs. approximately 12-fold, respectively). We conclude that transient prenatal androgen exposure produces features of the metabolic syndrome in adult female rats. Dyslipidemia and hepatic steatosis appear to be mediated by PA-induced increases in adiposity, whereas hyperinsulinemia appears to be a direct result of PA.
 ...
PMID:Transient prenatal androgen exposure produces metabolic syndrome in adult female rats. 1854 44

Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 +/- 0.42 g (VEH) versus 23.43 +/- 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 +/- 0.26 g (VEH) versus 19.78 +/- 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 +/- 0.48 g (VEH) versus 3.53 +/- 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 +/- 0.53 g (VEH) versus 4.57 +/- 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy.
 ...
PMID:A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health. 2057 26

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.
 ...
PMID:Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer. 3281 70

Androgen action generates sex-related differences that include changes in the gut microbiota composition. Hypoandrogenism and hyperandrogenism in males and females, respectively, are associated with the prevalence of metabolic disorders. Our recent work showed that male androgen receptor knockout (ARKO) mice developed high-fat diet (HFD)-dependent sarcopenic abdominal obesity, hyperglycemia, and hepatic steatosis, leading to early death. The ARKO mice also exhibited alterations in intestinal microbiota but did not experience metabolic abnormalities when administered with antibiotics. Here, we show that time-dependent changes in feed efficiency (ratio of body weight gain to food intake) and weight of dried feces-to-food ratio could be good markers for changes in gut microbiota. Turicibacter spp., Lactobacillus spp., and L. reuteri increased in the gut in both HFD-fed ARKO and castrated mice having metabolic abnormalities. HFD-fed ARKO mice showed increased plasma levels of aspartate, but not alanine, aminotransferase. Changes in the gut microbiome appear to provoke androgen deficiency-induced metabolic diseases, leading to early mortality.
 ...
PMID:Relationship between gut environment, feces-to-food ratio, and androgen deficiency-induced metabolic disorders. 3299 27