Raised Circulating Fetuin-A After 28-Day Overfeeding in Healthy Humans

Fetuin-A is a liver secretory glycoprotein that has been linked to the development of insulin resistance in animal models (1). Recent work suggests that free fatty acids (FFAs) and fetuin-A interact to induce insulin resistance in animal models (1) and humans (2). However, short-term overfeeding increases peripheral insulin resistance without significant increases in the levels of circulating FFAs in healthy humans (3,4). Thus, short-term overfeeding studies provide an ideal model with which to evaluate the relationships between fetuin-A and insulin resistance, independent of FFAs.We examined the effects of 28-day overfeeding (1,100 ± 100 kcal/day above baseline energy requirement, increasing mean [±SEM] dietary fat intake from 34 ± 1% to 45 ± 1% of energy intake) on circulating levels of fetuin-A, FFAs, and proinflammatory markers in healthy men and women (BMI 25.6 ± 0.6; age 37 ± 2 years; n = 40 [20 men]). The study protocol was described in detail previously (3 …