Increased oxidative stress precedes the onset of high-fat diet–induced insulin resistance and obesity

Abstract

Running title: oxidative stress induced by high-fat diet Key words: insulin resistance, oxidative stress, β-oxidation, NADPH oxidase Reprint requests to corresponding author. 1The abbreviations used are the following: HFD, high-fat diet; ROS, reactive oxygen species; PPARα, peroxisome proliferator-activated receptor-α; Nox, NADPH oxidase; FFAs, free fatty acids; Acox, acyl-CoA oxidase; CPT-1a, carnitine palmitoyltransferase 1a; CYP2E1, cytochrome P450 2E1; GTT, glucose tolerance test; Gpx, glutathione peroxidase; ITT, insulin tolerance test. 2 AbstractInsulin resistance is a key pathophysiological feature of metabolic syndrome. However, the initial events triggering the development of insulin resistance and its causal relations with dysregulation of glucose and fatty acids metabolism remain unclear. We investigated biological pathways that have the potential to induce insulin resistance in mice fed a high-fat diet (HFD). We demonstrate that the pathways for reactive oxygen species (ROS) production and oxidative stress are coordinately up-regulated in both the liver and adipose tissue of mice fed a HFD prior to the onset of insulin resistance through discrete mechanism. In the liver, a HFD up-regulated genes involved in sterol regulatory element binding protein-1c (SREBP-1c)-related fatty acid synthesis and peroxisome proliferator-activated receptor-α (PPARα)-related fatty acid oxidation. In the adipose tissue, however, the HFD down-regulated genes involved in fatty acid synthesis and up-regulated NADPH oxidase (Nox) complex. Furthermore, increased ROS production preceded the elevation of TNF-α and free fatty acids (FFAs) in the plasma and liver. ROS may be an initial key event triggering HFD-induced insulin resistance.

Maternal Obesity and Placental Oxidative Stress in the First Trimester

“…The second involves a priori increased NADPH oxidase activity in the placenta of obese women. In fact, NADPH oxidase appears to be the major contributor of ROS production in non-pregnant obese women [8,25,26]. Our findings differ from those earlier reported by Roberts et al [27] who found no direct relationship between lean, overweight, and obese BMI classes and oxidative stress [27].…”

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

“…The different timing of high cholesterol diet supply, either continuous or alternate, has a significant impact on HDL concentration level (about double in IHF, compared to HF cases), on Total Cholesterol/HDL ratio (more than double in HF compared to IHF group) as well as on TG concentration, significantly lower in IHF group. The amount of circulating LDL is reflected by a higher plasma concentration of oxLDL, with about sixfold increase compared to controls [37]. The same hypercholesterolemic plasma environment accounts for an increased expression of Apolipoprotein A1, especially in HF group, as previously reported [38] [39].…”

A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise

“…In animal studies, rats fed a high-sugar/high-fat diet had increased lipid peroxidation in the brain (Ribeiro et al, 2009, Stranahan et al, 2011, elevated plasma malondialdehyde (MDA) concentrations (a marker of lipid peroxidation) (Panchal et al, 2011) and increased mRNA expression levels of genes involved in ROS production in both the liver and adipose tissue (Matsuzawa-Nagata et al, 2008). In obese adults with metabolic syndrome, reducing energy intake by 2000kJ, mainly via carbohydrate restriction, was associated with decreased oxidative stress and increased levels of antioxidant markers, alpha-tocopherol and ceruloplasmin (Skalicky et al, 2009).…”