Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (Ser/Thr) phosphoproteins involved in leptin transduction mediate the effect of fructose on rat liver lipid metabolism

Abstract

There is controversy regarding whether fructose in liquid beverages constitutes another dietary ingredient of high caloric density or introduces qualitative changes in energy metabolism that further facilitate the appearance of metabolic diseases. Central to this issue is the elucidation of the molecular mechanism responsible for the metabolic alterations induced by fructose ingestion. Fructose administration (10% wt/vol) in the drinking water of Sprague-Dawley male rats for 14 days induced hyperleptinemia and hepatic leptin resistance. This was caused by impairment of the leptin-signal transduction mediated by both janus-activated kinase-2 and the mitogen-activated protein kinase pathway. The subsequent increase in activity in the liver of the unphosphorylated and active form of the forkhead box O1 nuclear factor, which transrepresses peroxisome proliferator-activated receptor ␣ activity, and a lack of activation of the adenosine monophosphate-activated protein kinase, led to hypertriglyceridemia and hepatic steatosis. These alterations are attributable to two key events: (1) F ructose makes up a significant proportion of energy in westernized diets, mainly due to the high intake of fructose-containing beverages. This situation has coincided with the growing prevalence of obesity and metabolic syndrome, recognized risk factors for cardiovascular diseases, over the past two decades. 1,2 Fructose in liquid diets induces hypertriglyceridemia to a greater extent than in solid diets. 3 A 10% dietary energy increase in

Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study

“…It is important to recognize that the observed ceramide and GlcCer‐lowering response associated with increased fruit and vegetable consumptions developed even though dietary fructose intake increased. Therefore, the ability of dietary fructose to augment ceramide synthesis likely depends on compromised hepatic function which was not evident in our investigation as demonstrated by clinically low concentrations of circulating triacylglycerol, VLDL‐cholesterol, AST, and ALT, as supported by Vila and coworkers (2008). …”

“…Although much of the data demonstrating the associative or causative relationship between ceramide and insulin resistance has been derived from high‐saturated fat‐feeding studies, Vilà et al. (2008) have established that hepatic ceramides are increased in rats fed fructose‐sweetened water. Vila and coworkers (2008) propose that the ability of fructose to promote ceramide synthesis may be attributed to impaired fatty acid β ‐oxidation.…”

“…(2008) have established that hepatic ceramides are increased in rats fed fructose‐sweetened water. Vila and coworkers (2008) propose that the ability of fructose to promote ceramide synthesis may be attributed to impaired fatty acid β ‐oxidation. Indeed, diets rich in refined carbohydrates such as those found in soft drinks can exacerbate NAFLD (Assy et al.…”

Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

“…Leptin is involved in the activation of AMPK and PPARa, both involved in the induction of fatty acid oxidation (Fruhbeck 2006). Further research is needed to address whether a saturated fat-rich diet induces fetal liver leptin resistance, inhibiting the activation of pathways triggered by leptin, which could lead to decreased fatty acid oxidation and thus lipid overaccumulation (Vila et al 2008).…”

Biomarker discovery of liver diseases using mass spectrometry-based metabolomics.

“…L-Threonine deficiency causes fat build up in the liver, while supplementation with L-threonine lowers hepatic fat concentration. [181]. L-Proline is a nonessential amino acid which can be synthesized from glutamate.…”