Can fructose influence the development of obesity mediated through hypothalamic alterations?

Abstract

Epidemiological data from the last decades point to an exponential growth in the number of obese people. Different behavioral factors, mainly associated with food consumption, appear to contribute significantly to its development. Concomitant with increased obesity rates, an increase in the consumption of fructose has been observed; therefore, fructose consumption has been implicated as an important obesogenic factor. However, changes in brain activity due to fructose consumption are possible, especially in relation to hypothalamic satiety mechanisms. In addition, the obese state may provide an environment of chronic inflammation and further contribute to the discontinuation of satiety mechanisms in the hypothalamus. We briefly review the intrinsic alterations to the increased adipose tissue, its connections with the hypothalamus in the control of energy signaling mechanisms and, consequently, the participation of fructose as a co‐adjuvant or trigger. Presenting the current context with clinical trials involving human and animal studies, we seek to contribute to a better understanding of the role of fructose in the progression of obesity.

Fructose Diet-Associated Molecular Alterations in Hypothalamus of Adolescent Rats: A Proteomic Approach

“…These results led us to hypothesize that the fructose-associated gain of S-100B is a trigger event driving hypothalamic inflammation. It is worth mentioning that hypothalamic inflammation is considered a potential trigger for the deregulation of mechanisms involved in food control and energy metabolism [ 28 , 83 , 84 ]. As a matter of fact, a long-term fructose diet was reported to induce increased IL-6 and TNF-alpha expression in mice hypothalamus, together with down-regulation of the expression of both the anorexigenic proopio-melanocortin (POMC) and the orexigenic NPY [ 85 ].…”

“…As a matter of fact, a long-term fructose diet was reported to induce increased IL-6 and TNF-alpha expression in mice hypothalamus, together with down-regulation of the expression of both the anorexigenic proopio-melanocortin (POMC) and the orexigenic NPY [ 85 ]. As above mentioned, several animal studies demonstrated the orexigenic effect of fructose [ 28 ]. Indeed, long-term fructose feeding in rats was associated with increased expression of the NPY gene [ 26 , 70 , 86 ], reduced POMC expression and impairment in the melanocortin system [ 26 ], and augmented gene expression of the agouti-related peptide [ 70 , 86 ].…”

“…Long-term fructose overfeeding was reported to alter the hypothalamic-pituitary-adrenal axis, thus causing glucocorticoid increase in peri-adolescent rats [ 22 ]. Further, fructose overconsumption was associated with impairment of hypothalamic insulin signaling [ 23 , 24 ], oxidative stress [ 24 , 25 ], and inflammation [ 23 , 26 , 27 ]; it was proposed that fructose-driven perturbations of hypothalamic function may alter the potential for satiety, thereby enhancing the possibility of developing obesity [ 28 ].…”

DNA methylation during human adipogenesis and the impact of fructose

“…8 Present Addresses: Vydiant Inc., Folsom, CA 95630, USA. 9 Present Address: CRCHU de Québec-Université Laval, Quebec City, Québec, Canada.…”

“…Fructose metabolism and the consequent effects on the regulation of host energy balance have been extensively studied in the gastrointestinal tract, kidney, and liver [25,64]. Human, laboratory animal, and cell culture systems have also demonstrated that fructose can be metabolized in the hypothalamus [9], innate immune system [83], cardiac and skeletal muscles ( [25,64], and adipose tissue and cells [25,64]. Excess fructose intake leads to the development of the multiple features of metabolic syndrome [7] including fatty liver, insulin resistance, diabetes, obesity, and hypertension [25].…”