Abstract

Dietary sugar has been recognized both by basic research and epidemiological studies as an important player in the current epidemics of obesity and metabolic syndrome. Our lab is focused on identifying potential mechanisms that we can target to prevent or even treat multiple features associated with this condition (obesity, diabetes, fatty liver, dyslipidemia or high blood pressure) as well as with alcoholism and alcoholic liver disease. In particular, our research has discovered that the metabolism of dietary sugar (as in sodas), and specifically, fructose is directly linked to metabolic dysfunction, oxidative stress and inflammation and is also responsible for craving and the hedonic pleasure associated with sugar and alcohol intake. Furthermore, our lab has demonstrated that besides its dietary source, fructose can be produced in the body and that the metabolism of this endogenous fructose is an important deleterious step in the pathogenesis of kidney disease, both in acute kidney injury (as it would occur with radiocontrast agents or dehydration) and chronic kidney disease (as in diabetic kidney disease). To this end, we employ both genetic (like leptin-receptor knockouts) and diet-induced (high sugar, high fat or western diets) models to induce metabolic syndrome as well as alcohol-binging models and we characterize the specific response of mice deficient in proteins involved in the metabolism of fructose (fructokinase and aldolase b). We have developed tissue-specific and inducible models to knock down these proteins in those organs that we believe are key in the pathogenesis of metabolic syndrome (liver, intestine, adipose tissue and brain/neurons) and we are now in the process of characterizing the role of these proteins in such organs.