title: High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria.
abstract: Obesity, a risk factor for insulin resistance, contributes to the development of type 2 diabetes and cardiovascular diseases. The relationship between increased levels of free fatty acids in the liver mitochondria, mitochondrial function, and ROS generation in rat model of obesity induced by a high-sucrose diet was not sufficiently established. We determined how the bioenergetic functions and ROS generation of the mitochondria respond to a hyperlipidemic environment. Mitochondria from sucrose-fed rats generated H(2)O(2) at a higher rate than the control mitochondria. Adding fatty acid-free bovine serum albumin to mitochondria from sucrose-fed rats significantly reduced the rate of H(2)O(2) generation. In contrast, adding exogenous oleic or linoleic acid exacerbated the rate of H(2)O(2) generation in both sucrose-fed and control mitochondria, and the mitochondria from sucrose-fed rats were more sensitive than the control mitochondria. The increased rate of H(2)O(2) generation in sucrose-fed mitochondria corresponded to decreased levels of reduced GSH and vitamin E and increased levels of Cu/Zn-SOD in the intermembrane space. There was no difference between the levels of lipid peroxidation and protein carbonylation in the two types of mitochondria. In addition to the normal activity of Mn-SOD, GPX and catalase detected an increased activity of complex II, and upregulation of UCP2 was observed in mitochondria from sucrose-fed rats, all of which may accelerate respiration rates and reduce generation of ROS. In turn, these effects may protect the mitochondria of sucrose-fed rats from oxidative stress and preserve their function and integrity. However, in whole liver these adaptive mechanisms of the mitochondria were inefficient at counteracting redox imbalances and inhibiting oxidative stress outside of the mitochondria.
authors.affiliation: Cardiovascular Biomedicine, Cellular Biology, National Institute of Cardiology Ignacio Chávez, Tlalpan, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Ruiz-Ramírez
authors.forename: Monserrath
authors.initials: M
authors.lastname: Chávez-Salgado
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Peñeda-Flores
authors.forename: Estrella
authors.initials: E
authors.lastname: Zapata
authors.forename: Felipe
authors.initials: F
authors.lastname: Masso
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Hafidi
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019422:Dietary Sucrose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D017494:Proton Pumps / Q000378:metabolism; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071246:Uncoupling Protein 2
chemical_list: D019422:Dietary Sucrose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017494:Proton Pumps; D011522:Protons; D017382:Reactive Oxygen Species; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2