Low-Concentration Sucrose Intake During Puberty Alters Cholesterol Metabolism and Circulating Testosterone Levels in Male Mice

Background: Pubertal sucrose intake is a public health concern, but its effects on cholesterol metabolism and male reproductive endocrinology remain poorly understood. Rodent studies of this window have generally used 30% (w/v) sucrose or 20% (w/v) fructose solutions; beverage-like concentrations have been examined less often. Reported effects of dietary sugar on circulating testosterone are inconsistent; we hypothesized that differences in developmental stage might account for this discrepancy. Methods: Male ICR (Institute of Cancer Research) mice had free access to a 10% (w/v) sucrose solution from 4 to 8 weeks of age. We assessed hepatic and plasma lipids, testicular cholesterol and testosterone, hepatic acetyl-CoA carboxylase (ACC) and AMPK phosphorylation, and expression of cholesterol metabolism- and steroidogenesis-related genes. All measurements were performed after a 16 h fast, during which the sucrose solution was replaced with water. Results: Sucrose selectively elevated hepatic and plasma cholesterol without altering triglycerides, the circulating increase being confined to the non-high-density lipoprotein fraction. Phosphorylation of ACC1 and ACC2 rose while AMPK phosphorylation was unchanged. Peritesticular fat weight increased despite unchanged body weight and energy intake. In the testes, cholesterol content and several steroidogenic transcripts increased, whereas steroidogenic enzyme protein was unchanged. Plasma testosterone increased, whereas intratesticular testosterone did not. Conclusions: In male ICR mice, a 10% (w/v) sucrose solution during puberty supplied approximately 25% of total energy intake, with a comparable fall in solid-chow intake; it was associated with a cholesterol-predominant rather than triglyceride-predominant lipid response and higher circulating testosterone. Testicular cholesterol content and plasma testosterone were both higher while steroidogenic enzyme protein was unchanged, indicating an association between the two rather than a change in steroidogenic capacity.