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Dyslipidemia in metabolic syndrome is necessary to elicit severe coronary artery disease and non‐alcoholic steatohepatitis
Author(s) -
Neeb Zachary P,
Alloosh Mouhamad,
Saxena Romil,
Chalasani Naga,
Sturek Michael
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.789.5
Subject(s) - steatohepatitis , dyslipidemia , metabolic syndrome , medicine , coronary artery disease , fatty liver , endocrinology , insulin resistance , obesity , disease
Risk of coronary artery disease (CAD) is increased in patients with metabolic syndrome (MetS) and non‐alcoholic steatohepatitis (NASH); however, the relative importance of each component of MetS (i.e. obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension) is unknown. We hypothesized that occlusive and complex CAD and NASH are primarily driven by dyslipidemia within the MetS milieu and that all other components of MetS combined are not sufficient. Ossabaw swine were fed standard chow (Lean; N=16), chow with f ructose (FMetS; N=9), t rans‐fat/cholesterol/fructose (TMetS; N=14), or m ixed‐source fat/cholesterol/fructose (MMetS; N=6) for 22 weeks. FMetS developed normolipidemic MetS. TMetS, and to a greater extent MMetS, developed MetS with the dyslipidemia component. Lean demonstrated mild CAD and no NASH. Although FMetS developed MetS CAD and NASH were virtually non‐existent. CAD and liver disease were directly related to dyslipidemia in MetS, with TMetS showing fatty/fibrous atheroma and MMetS progressing to stenotic, diffuse, and complex CAD and NASH. Total monounsaturated/polyunsaturated fatty acid ratio and fatty acid metabolism enzyme indices were associated with CAD and NASH, however LDL gram‐years most reliably predicted CAD and NASH. Thus, dyslipidemia was a necessary component of MetS for eliciting severe CAD and NASH in swine that superbly mimic human pathologies.