Low-Fat by Formulation, Not by Benefit: A Purified Low-Fat Diet Is Associated with Gut–Liver–Kidney Alterations in Rats

Background/Objectives: “Low-fat” claims are defined by a fat threshold, with no requirements regarding the nutrients replacing fat. Reformulation often relies on refined starches and free sugars at the expense of dietary fiber. Thus, a low-fat (LF) product is not necessarily of good carbohydrate quality, a dimension that macronutrient-based classification fails to capture. Whether LF-derived poor carbohydrate quality is associated with organ-specific alterations across the gut–liver–kidney axis remains unknown. Methods: Male Wistar rats were fed for 24 weeks a purified LF diet, its ingredient-matched purified high-fat, high-sucrose counterpart (HF), or a whole-grain Chow reference of similar energy density. Carbohydrate quality was assessed using the carbohydrate-to-dietary fiber-to-free sugars ratio. Body weight and adiposity, glucose homeostasis, gut fermentation, and hepatic and renal functional and structural parameters were evaluated. Results: Only Chow met the 10:1:1 carbohydrate quality criterion. At a caloric intake that did not exceed that of Chow, LF feeding was associated with increased body weight, adipocyte hypertrophy, impaired glucose tolerance and postprandial hyperinsulinemia. Fecal short-chain fatty acids (SCFAs) and branched SCFAs declined, consistent with a reduction in colonic fermentative output. Chronic LF exposure was additionally associated with hepatic and renal lipid accumulation, normoglycemic glycosuria, and podocyte structural alterations. Conclusions: A purified low-fat diet was associated with the same spectrum of gut, liver and kidney alterations as its high-fat counterpart, without excess caloric intake. These findings support an important role for nutrient sources and carbohydrate quality in shaping metabolic health beyond dietary fat content or caloric load alone.