Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insufficient hepatic O2 in animal and human studies has been shown to elicit a hepatorenal reflex in response to increased hepatic adenosine, resulting in stimulation of renal as well as muscle sympathetic nerve activity and activating the renin angiotensin system. Low hepatic ATP, hyperuricemia, and hepatic lipid accumulation reported in metabolic syndrome (MetS) patients may reflect insufficient hepatic O2 delivery, potentially accounting for the sympathetic overdrive associated with MetS. This theoretical concept is supported by experimental results in animals fed a high fructose diet to induce MetS. Hepatic fructose metabolism rapidly consumes ATP resulting in increased adenosine production and hyperuricemia as well as elevated renin release and sympathetic activity. This review makes the case for the hepatorenal reflex causing sympathetic overdrive and metabolic syndrome in response to exaggerated splanchnic oxygen consumption from excessive eating. This is strongly reinforced by the fact that MetS is cured in a matter of days in a significant percentage of patients by diet, bariatric surgery, or endoluminal sleeve, all of which would decrease splanchnic oxygen demand by limiting nutrient contact with the mucosa and reducing the nutrient load due to the loss of appetite or dietary restriction.
...
PMID:Metabolic syndrome and the hepatorenal reflex. 2830 1

Insufficient hepatic O2 in animal and human studies has been shown to elicit a hepatorenal reflex in response to increased hepatic adenosine, resulting in the stimulation of renal as well as muscle sympathetic nerve activity and activating the renin angiotensin system. Low hepatic ATP, hyperuricemia, and hepatic lipid accumulation reported in metabolic syndrome (MetS) patients may reflect insufficient hepatic O2 delivery, potentially accounting for the sympathetic overdrive associated with MetS. This theoretical concept is supported by experimental results in animals fed a high fructose diet to induce MetS. Hepatic fructose metabolism rapidly consumes ATP resulting in increased adenosine production and hyperuricemia as well as elevated renin release and sympathetic activity. This review makes the case for the hepatorenal reflex causing sympathetic overdrive and metabolic syndrome in response to exaggerated splanchnic oxygen consumption from excessive eating. This is strongly reinforced by the fact that MetS is cured in a matter of days in a significant percentage of patients by diet, bariatric surgery, or endoluminal sleeve, all of which would decrease splanchnic oxygen demand by limiting nutrient contact with the mucosa and reducing the nutrient load due to loss of appetite or dietary restriction.
 ...
PMID:Metabolic syndrome and the hepatorenal reflex. 2816 86

Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems' metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.
 ...
PMID:Therapeutic Potential of Targeting the Ghrelin Pathway. 2839 33

Cancer and its treatment can lead in men to testosterone deficiency, accompanied by somatic and mental symptoms. Germ cell tumours and their treatment may disturb the pituitary-gonadal axis, hence leading to significant clinical abnormalities. In some prostate cancer patients, castration, temporary or permanent, is a desired therapeutic condition. Yet, it is burdened with various side effects of complex intensity and significance. Last but not least, patients in the terminal stage of a malignancy present with low testosterone concentrations as a part of anorexia-cachexia syndrome. Oncological management of such patients disturbs their homeostasis, androgen metabolism included, which results in numerous complications and worsens their quality of life. In the present paper, we analysed the frequency and sequelae of testosterone deficiency in some clinical scenarios, on the basis of original papers, meta-analyses and reviews available in PubMed. Androgen secretion disorders in male cancer patients depend on a cancer type, stage and methods of treatment. Number of testicular cancer survivors is increasing, and as a consequence, more patients cope with late complications, testosterone deficiency included. Hormone therapy in prostate cancer patients significantly prolongs survival, and then numerous men experience long-term adverse effects of androgen deficiency. Those, in turn, particularly the metabolic syndrome, may contribute to increased mortality. Androgen deficiency is a part of cancer anorexia-cachexia syndrome. The role of androgen deficiency in cancer patients is still under debate, and further studies are urgently needed to establish appropriate clinical guidelines.
 ...
PMID:Clinical significance of androgen secretion disorders in men with a malignancy. 2857 37

Sarcopenia is defined as a combination of low muscle mass with low muscle function. The term was first used to designate the loss of muscle mass and performance associated with aging. Now, recognized causes of sarcopenia also include chronic disease, a physically inactive lifestyle, loss of mobility, and malnutrition. Sarcopenia should be differentiated from cachexia, which is characterized not only by low muscle mass but also by weight loss and anorexia. Sarcopenia results from complex and interdependent pathophysiological mechanisms that include aging, physical inactivity, neuromuscular compromise, resistance to postprandial anabolism, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, mitochondrial dysfunction, and inflammation. The prevalence of sarcopenia ranges from 3% to 24% depending on the diagnostic criteria used and increases with age. Among patients with rheumatoid arthritis 20% to 30% have sarcopenia, which correlates with disease severity. Sarcopenia exacts a heavy toll of functional impairment, metabolic disorders, morbidity, mortality, and healthcare costs. Thus, the consequences of sarcopenia include disability, quality of life impairments, falls, osteoporosis, dyslipidemia, an increased cardiovascular risk, metabolic syndrome, and immunosuppression. The adverse effects of sarcopenia are particularly great in patients with a high fat mass, a condition known as sarcopenic obesity. The diagnosis of sarcopenia rests on muscle mass measurements and on functional tests that evaluate either muscle strength or physical performance (walking, balance). No specific biomarkers have been identified to date. The management of sarcopenia requires a multimodal approach combining a sufficient intake of high-quality protein and fatty acids, physical exercise, and antiinflammatory medications. Selective androgen receptor modulators and anti-myostatin antibodies are being evaluated as potential stimulators of muscle anabolism.
 ...
PMID:Sarcopenia. 3211 90

Everolimus is administered to patients with metastatic renal cell carcinoma in full daily dose of 10 mg or in reduced daily dose of 5 mg in case adverse effect occurred. These include metabolic adverse effects, mucositis, anorexia, and non-infectious pneumonitis and lead to increase in morbidity and decrease in the quality of life of the patient. Our goal was to evaluate the administration of fenofibrate and metformin in everolimus induced hypertriglyceridemia and hyperglycemia. The role of mTOR in lipid and glucose metabolism was researched in literature. The effect of including fenofibrate and metformin into metabolic adverse effect management guidelines in metastatic renal cell carcinoma patients who are administered everolimus was evaluated. Fenofibrate, metformin, and everolimus have several similar effects on intracellular level, therefore the effect of fenofibrate and metformin in treating everolimus induced metabolic adverse effects in metastatic renal cell carcinoma patients may be limited. The manifestation of metabolic adverse effects in patients treated with everolimus is not identical with metabolic syndrome or type II diabetes in standard population.
 ...
PMID:Management of metabolic adverse effects of everolimus in patients with renal carcinoma. 3199 97

Microglia in the mediobasal hypothalamus (MBH) respond to inflammatory stimuli and metabolic perturbations to mediate body composition. This concept is well studied in the context of high fat diet induced obesity (HFDO), yet has not been investigated in the context of cachexia, a devastating metabolic syndrome characterized by anorexia, fatigue, and muscle catabolism. We show that microglia accumulate specifically in the MBH early in pancreatic ductal adenocarcinoma (PDAC)-associated cachexia and assume an activated morphology. Furthermore, we observe astrogliosis in the MBH and hippocampus concurrent with cachexia initiation. We next show that circulating immune cells resembling macrophages infiltrate the MBH. PDAC-derived factors induced microglia to express a transcriptional profile in vitro that was distinct from that induced by lipopolysaccharide (LPS). Microglia depletion through CSF1-R antagonism resulted in accelerated cachexia onset and increased anorexia, fatigue, and muscle catabolism during PDAC. This corresponded with increased hypothalamic-pituitary-adrenal (HPA) axis activation. CSF1-R antagonism had little effect on inflammatory response in the circulation, liver, or tumor. These findings demonstrate that microglia are protective against PDAC cachexia and provide mechanistic insight into this function.
 ...
PMID:Microglia in the hypothalamus respond to tumor-derived factors and are protective against cachexia during pancreatic cancer. 3203 22


<< Previous 1 2 3