Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dyslipidemia of the metabolic syndrome is associated with alterations in triglyceride and high-density lipoprotein (HDL) metabolism. We examined the serum levels of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor HDL-associated protein, in a cohort with a wide range of insulin sensitivity. The mean serum GPI-PLD mass from 109 subjects was 58.9 +/- 18.4 microg/mL (mean +/- SD). GPI-PLD levels directly correlated with cholesterol, apolipoprotein AI, triglycerides, insulin, and homeostasis model assessment (HOMA) but not C-reactive protein. These results suggest that increased serum GPI-PLD is associated with the insulin resistance.
 ...
PMID:Insulin resistance is associated with increased serum levels of glycosylphosphatidylinositol-specific phospholipase D. 1476 61

Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure and contributes to cardiovascular and renal disease, stroke and visual loss. Hypertension is also associated with obesity, which is correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear. Several studies have suggested that aldosterone levels are elevated with obesity and may represent a link between obesity and hypertension. In addition to hypertension, obese patients typically have dyslipidemia, including elevated serum levels of very low-density lipoprotein (VLDL). VLDL, which functions to transport triglycerides from the liver to peripheral tissues, has been demonstrated to stimulate aldosterone production. Recent studies suggest that the signaling pathways activated by VLDL are similar to those utilized by AngII. Thus, VLDL increases cytosolic calcium levels and stimulates phospholipase D (PLD) activity to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression. These effects seem to be mediated by the ability of VLDL to increase the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element-binding (CREB) protein family of transcription factors. Thus, research into the pathways by which VLDL stimulates aldosterone production may identify novel targets for the development of therapies for the treatment of hypertension, particularly those associated with obesity, and other aldosterone-modulated pathologies.
 ...
PMID:Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production. 2791 72

Significance: Cardiometabolic disorders (CMD) are composed of a plethora of metabolic dysfunctions such as dyslipidemia, nonalcoholic fatty liver disease, insulin resistance, and hypertension. The development of these disorders is highly linked to inflammation and oxidative stress (OxS), two metabolic states closely related to physiological and pathological conditions. Given the drastically rising CMD prevalence, the discovery of new therapeutic targets/novel nutritional approaches is of utmost importance. Recent Advances: The tremendous progress in methods/technologies and animal modeling has allowed the clarification of phospholipase D (PLD) critical roles in multiple cellular processes, whether directly or indirectly via phosphatidic acid, the lipid product mediating signaling functions. In view of its multiple features and implications in various diseases, PLD has emerged as a drug target. Critical Issues: Although insulin stimulates PLD activity and, in turn, PLD regulates insulin signaling, the impact of the two important PLD isoforms on the metabolic syndrome components remains vague. Therefore, after outlining PLD1/PLD2 characteristics and functions, their role in inflammation, OxS, and CMD has been analyzed and critically reported in the present exhaustive review. The influence of functional foods and nutrients in the regulation of PLD has also been examined. Future Directions: Available evidence supports the implication of PLD in CMD, but only few studies emphasize its mechanisms of action and specific regulation by nutraceutical compounds. Therefore, additional investigations are first needed to clarify the functional role of nutraceutics and, second, to elucidate whether targeting PLDs with food compounds represents an appropriate therapeutic strategy to treat CMD.
 ...
PMID:Phospholipase D As a Potential Modulator of Metabolic Syndrome: Impact of Functional Foods. 3258 6