There are an increasing number of alcoholic beverages moving from sweetening their drinks with sugar to artificial sweeteners like sucralose to cut the caloric content of their drinks, while maintaining a sweet flavor. Despite independent links between alcohol, sucrose, and sucralose to metabolic dysfunction, as well as the common practice of drinking alcohol mixed with sugary or artificially sweetened beverages, there is a lack of research assessing their combined effects. This is of concern, as endoplasmic reticulum (ER) stress is a known mediator in pathways of insulin and leptin resistance. The overall goal of this work is to provide insight into the effects of these beverage combinations on brain health and resulting metabolic consequences. To address this gap, we performed a mouse feeding study to observe impacts on hypothalamic genes associated with inflammation and ER stress. Young (6-week-old) female C57BL6 mice were split into six groups: control, sucralose (0.5% w/v), sugar (10% w/v), ethanol (10% w/v), sucralose/ethanol, or sugar/ethanol. Early analyses show a trend towards higher glucose in all mice consuming ethanol, regardless of sweetener, and increased glutathione in peripheral organs in those consuming sucralose/ethanol. Currently we are assessing key genes in hypothalamic dysfunction (ATF6, PERK/ATF4, IRE1a/XBP1, CHOP and BAK) and performing standard assays of pro- and antioxidant status with results forthcoming. We anticipate differential sweetener and ethanol combinations will result in varying levels of hypothalamic dysfunction. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Sherman et al. (Fri,) studied this question.