January 10th, 2018
Insulin Resistance in Metabolic Syndrome – Leptin resistance
Other obesity-linked mechanisms explaining insulin resistance have been attributed to fructose-induced leptin resistance. In a study  reviewing the link between obesity and insulin resistance, it is for instance observed that insulin resistance features predominantly in mouse strains deficient in leptin or those where expression of leptin receptors is knocked down. When leptin is administered to such mouse – deficient in leptin – systemic glucose and insulin levels have been noted to decrease rapidly . Thus leptin has a core role in sensitization of cells to insulin, a process thought to occur either through leptin’s actions at the CNS that, for instance, result in alterations in food intake or through direct signaling effects at tissue-sites where insulin functions .
In relation to fructose, intake of fructose has been associated with leptin resistance. In a study conducted with male Sprague Dawley rats, chronic consumption of fructose was associated with resistance to leptin, despite serum levels of leptin, weight and adiposity profiles being comparable between control and fructose-treated rats . In the control (fructose-free) rats intraperitoneal injections of leptin was associated with reduced 24-h food intake but such association was not noted for the test (fructose-treated) rats. Such lack of satiety response from test rats was associated with a 25.7% reduction signaling mechanisms operating in the hypothalamus [11, p. R1370). Accordingly, fructose-mediated insulin resistance could arise through its effect of promoting resistance of cells to leptin.
The effect of fructose in mediating insulin resistance can thus arise from various obesity-related mechanisms. Primary among these are those favoring fructose induced lipogenesis, which is favored by the fact that fructose metabolism bypasses a core regulatory stage (one catalyzed by PFK), that is essential in maintaining metabolites in the glycolytic pathway at optimal revels. Particularly, such implication is noted with association of increased intake of HFCS used as a sweetener in food and beverage industry, with increased cases of obesity [1,3], despite other findings that such contribution may not be significantly different from that of other energy sources . Other associations however exist with regard to fructose implication in leptin resistance , a condition suggested to lead to insulin resistance . Go to hyperuracemia.