Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets.

BACKGROUND: PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. METHODS: We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1). FINDINGS: HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman's correlations revealed that plasma PCSK9 concentrations upon 7-day HFruc1 diet were positively associated with plasma triglycerides (r=0.54, p=0.01) and IHCL (r=0.56, p=0.001), and inversely correlated with hepatic (r=0.54, p=0.014) and whole-body (r=-0.59, p=0.0065) insulin sensitivity. CONCLUSIONS: Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, November 2002

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Center for Sustainable Agriculture, Annual Report 1997-1998

The Leopold Center was established by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. Its mandated missions are to identify impacts of agricultural practices, contribute to the development of profitable farming systems that conserve natural resources, and cooperate with Iowa State University Extension to inform the public of new findings.Information for this report was compiled by Leopold Center staff with the help of its researchers and educators who are committed to improving Iowa agriculture and the lives of Iowans.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Fall 2004

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Winter 2004

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Fall 2005

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Spring 2005

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Summer 2005

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Winter 2005

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Fall 2006

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.

Leopold Letter: A Newsletter of the Leopold Center for Sustainable Agriculture, Spring 2006

The Leopold Center was created by the Iowa Legislature as part of the Iowa Groundwater Protection Act of 1987. The Leopold Center believes contribute to a healthy ways of thinking about markets for Iowa farmers, a better understanding of local ecosystems, public policies and economic practices, and partnerships with consumers.