Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human

BACKGROUND: Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. OBJECTIVES: In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. METHODS: 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. RESULTS: We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. CONCLUSIONS: Our data provide the first evidence that obesity and metabolic syndrome are associated with major, gender-specific, changes in circulating oxysterols and fatty acids. These findings suggest a metabolic link between oxysterols and fatty acids, and that oxysterols may contribute to the epidemic diseases associated with obesity and metabolic syndrome in female

N3 Fatty Acids and Neurodegeneration: Is it Enough to Stop or to Shift?

A recent large intervention study has showed no effect of dietary doses of n3 fatty acids (FA) on global cognitive decline in coronary heart disease patients [1]. N3-FA, which include α-linoleic acid, eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) (Figure 1), have been subject of intense investigation in the recent years for expected benefits in delaying cognitive decline. Previous epidemiological and experimental animal studies suggested that deficiency in n3-FA, in particular DHA that is one of the most represented fatty acid in the brain, accelerates cognitive decline and increases the risk of developing AD [2-7]. With the Geleijnse’s trial, is it enough to suggest stopping investigation on n3-FA in the context of cognitive decline in man

Antioxidants and Cognitive Function: Misleading Concepts and New Strategies

In a recent study, Yasuno et al. [1] reported promising results over the improvement of cognitive function by a combination of antioxidants in patients more than 65 years old. Forty-one patients with deterioration of cognitive function were evaluated after 3 years of follow up, during which patients undertook “antioxidant” supplementation. As a control, data of 622 patients without supplement intake were collected. The authors found that “antioxidants” improved cognitive function, arguing that antioxidants used in combination act synergistically in ameliorating cognitive function. According to author’s definition, supplement intake included a daily dose of 1182 mg n-3 fatty acids (FA), 83 mg lycopene from tomato extracts, and 240 mg Ginkgo Biloba leaf extract. In detail, n3-FA consisted of 1.182 mg purified fish oil, containing 290 mgeicosapentaenoic acid (EPA) and 203 mg docosahexaenoic acid (DHA)

IL-6-Producing, noncatecholamines secreting pheochromocytoma presenting as fever of unknown origin

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared

Plasma fatty acid lipidome is associated with cirrhosis prognosis and graft damage in liver transplantation

Knowledge regarding the plasma fatty acid (FA) pattern in patients with liver cirrhosis is fragmentary.OBJECTIVE: We evaluated plasma FA lipidome and its association with the prognosis of cirrhosis and severity of liver graft damage after transplantation.DESIGN: In this observational study, plasma FA lipidome was investigated in 51 cirrhotic patients before liver transplantation and in 90 age- and sex-matched healthy control subjects. In addition, we studied ischemia-reperfusion damage in the liver of 38 patients for whom a graft biopsy was available at transplantation. With the use of logistic regression, we modeled the presence of cirrhosis, the dichotomized model for end-stage liver disease score below and above the median, and the presence of severe liver graft ischemia-reperfusion damage.RESULTS: The FA pattern was markedly altered in cirrhotic patients, who showed, compared with healthy controls, higher monounsaturated FAs, lower n-6 and n-3 polyunsaturated FAs, and undetectable cerotic acid. Plasma di-homo-γ-linolenic acid was independently associated with the presence of cirrhosis (OR: 0.026; 95% CI: 0.004, 0.196; P < 0.0001), severity of its prognosis (OR: 0.041; 95% CI:0.005, 0.376; P = 0.006), postreperfusion graft hepatocellular necrosis (OR: 0.921; 95% CI: 0.851, 0.997; P = 0.043), and sinusoidal congestion (OR: 0.954; 95% CI: 0.912, 0.998; P = 0.039). Associations of di-homo-γ-linolenic acid with the presence of cirrhosis and severity of its prognosis were confirmed also after false discovery rate correction.Conclusions: Cerotic and di-homo-γ-linolenic acids may serve as markers of disease and prognosis in liver cirrhosis. Dietary supplementation with di-homo-γ-linolenic acid could be a reasonable interventional strategy to delay disease progression in liver cirrhosis. This trial was registered at clinicaltrials.gov as NCT01389115

Plasma fatty acid lipidome is associated with cirrhosis prognosis and graft damage in liver transplantation

Knowledge regarding the plasma fatty acid (FA) pattern in patients with liver cirrhosis is fragmentary.OBJECTIVE: We evaluated plasma FA lipidome and its association with the prognosis of cirrhosis and severity of liver graft damage after transplantation.DESIGN: In this observational study, plasma FA lipidome was investigated in 51 cirrhotic patients before liver transplantation and in 90 age- and sex-matched healthy control subjects. In addition, we studied ischemia-reperfusion damage in the liver of 38 patients for whom a graft biopsy was available at transplantation. With the use of logistic regression, we modeled the presence of cirrhosis, the dichotomized model for end-stage liver disease score below and above the median, and the presence of severe liver graft ischemia-reperfusion damage.RESULTS: The FA pattern was markedly altered in cirrhotic patients, who showed, compared with healthy controls, higher monounsaturated FAs, lower n-6 and n-3 polyunsaturated FAs, and undetectable cerotic acid. Plasma di-homo-γ-linolenic acid was independently associated with the presence of cirrhosis (OR: 0.026; 95% CI: 0.004, 0.196; P < 0.0001), severity of its prognosis (OR: 0.041; 95% CI:0.005, 0.376; P = 0.006), postreperfusion graft hepatocellular necrosis (OR: 0.921; 95% CI: 0.851, 0.997; P = 0.043), and sinusoidal congestion (OR: 0.954; 95% CI: 0.912, 0.998; P = 0.039). Associations of di-homo-γ-linolenic acid with the presence of cirrhosis and severity of its prognosis were confirmed also after false discovery rate correction.Conclusions: Cerotic and di-homo-γ-linolenic acids may serve as markers of disease and prognosis in liver cirrhosis. Dietary supplementation with di-homo-γ-linolenic acid could be a reasonable interventional strategy to delay disease progression in liver cirrhosis. This trial was registered at clinicaltrials.gov as NCT01389115