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Excess dietary sucrose is associated with obesity and metabolic diseases. This relationship is driven by the malfunction of several cell types and tissues critical for the regulation of energy balance, including hypothalamic neurons and white adipose tissue (WAT). However, the mechanisms behind these effects of dietary sucrose are still unclear and might be independent of increased adiposity. Accumulating evidence has indicated that dysregulation of autophagy, a fundamental process for maintenance of cellular homeostasis, alters energy metabolism in hypothalamic neurons and WAT, but whether autophagy could mediate the detrimental effects of dietary sucrose on hypothalamic neurons and WAT that contribute to weight gain is a matter of debate. In this review, we examine the hypothesis that dysregulated autophagy in hypothalamic neurons and WAT is an adiposity-independent effect of sucrose that contributes to increased body weight gain. We propose that excess dietary sucrose leads to autophagy unbalance in hypothalamic neurons and WAT, which increases caloric intake and body weight, favoring the emergence of obesity and metabolic diseases.