Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. It increases a risk of cardiovascular and metabolic diseases such as diabetes, hypertension, and hyperlipidemia. Recent molecular genetic studies have disclosed some monogenic forms of obesity in humans. Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor.
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PMID:[Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. 1185 34

Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact.
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PMID:Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism. 1893 94

Glucocorticoids mediate numerous essential processes in the human body via binding to the glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and GR antagonists can be used to treat many symptoms of glucocorticoid-induced pathology. The purpose of this study was to characterize the tissue-specific properties of the selective GR antagonist CORT125281. We evaluated the antagonistic effects of CORT125281 upon acute and subchronic corticosterone exposure in mice. In the acute corticosterone setting, hypothalamus-pituitary-adrenal-axis activity was investigated by measurement of basal- and stress-induced corticosterone levels, adrenocorticotropic hormone levels and pituitary proopiomelanocortin expression. GR signaling was evaluated by RT-PCR analysis of GR-responsive transcripts in liver, muscle, brown adipose tissue (BAT), white adipose tissue (WAT) and hippocampus. Pretreatment with a high dose of CORT125281 antagonized GR activity in a tissue-dependent manner. We observed complete inhibition of GR-induced target gene expression in the liver, partial blockade in muscle and BAT and no antagonism in WAT and hippocampus. Tissue distribution only partially explained the lack of effective antagonism. CORT125281 treatment did not disinhibit the hypothalamus-pituitary-adrenal neuroendocrine axis. In the subchronic corticosterone setting, CORT125281 partially prevented corticosterone-induced hyperinsulinemia, but not hyperlipidemia and immune suppression. In conclusion, CORT125281 antagonizes GR transcriptional activity in a tissue-dependent manner and improves corticosterone-induced hyperinsulinemia. Tailored dosing of CORT125281 may allow tissue-specific inhibition of GR transcriptional activity.
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PMID:The selective glucocorticoid receptor antagonist CORT125281 has tissue-specific activity. 3236 74