title: Carob pod insoluble fiber exerts anti-atherosclerotic effects in rabbits through sirtuin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α.
abstract: The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g ⋅ kg(-1) ⋅ d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g ⋅ kg(-1) ⋅ d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-β (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of SIRT1 and PGC-1α (160% and 121% of the control group, respectively; P < 0.05) vascular expression. In summary, we demonstrated for the first time, to our knowledge, that administration of IFC reduces the development of atherosclerosis in rabbits. This effect seems to be related to an improvement in endothelial function and a reduction of inflammation and fibrosis, most probably as a consequence of the reduction of serum concentrations of cholesterol and triglycerides. Increased expression of aortic SIRT1 and PGC-1α could play an important role in the observed effects of IFC in rabbits with dyslipidemia.
authors.affiliation: Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Valero-Muñoz
authors.affiliation: Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Fernández
authors.affiliation: Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ballesteros
authors.affiliation: Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.affiliation: Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain nataliaheras@med.ucm.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002791:Cholesterol, Dietary / Q000494:pharmacology; D000074263:Coconut Oil; D059305:Diet, High-Fat; D004043:Dietary Fiber / Q000494:pharmacology / Q000627:therapeutic use*; D019587:Dietary Supplements; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004730:Endothelium, Vascular / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005355:Fibrosis; D005638:Fruit; D005685:Galactans / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008351:Mannans / Q000494:pharmacology / Q000627:therapeutic use*; D047495:PPAR gamma / Q000097:blood; D053149:Plant Gums / Q000494:pharmacology / Q000627:therapeutic use*; D010938:Plant Oils / Q000494:pharmacology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011817:Rabbits; D056564:Sirtuin 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000097:blood*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002791:Cholesterol, Dietary; D004043:Dietary Fiber; D005685:Galactans; D018836:Inflammation Mediators; D008351:Mannans; D047495:PPAR gamma; D053149:Plant Gums; D010938:Plant Oils; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D056564:Sirtuin 1; D000074263:Coconut Oil; C017471:locust bean gum