Cafeteria and Fast-Food Diets Induce Neuroinflammation, Social Deficits, but a Different Cardiometabolic Phenotype

Obesity is a risk factor for several non-communicable diseases and premature death. The Western-type diet, rich in calories and diverse in tastes, smells, and textures, promotes the onset and progression of obesity. We compared the effects of two Western-style palatable obesogenic diets-the cafeteria (CAF) diet, which allows for self-selection of calorie-dense food items consumed by humans, and the fast-food diet (FFD)-composed of a fixed combination of cheeseburgers and fries-on the manifestation of obesity-related complications.

3-month-old female rats consumed either the control (CTRL), FFD, or CAF diet for 12 months. Body weight was monitored weekly. At the end of the experiment, rats underwent metabolic and behavioral testing. Cardiometabolic markers and those characterizing glycoxidative and carbonyl stress, inflammatory status, and tryptophan metabolism were determined.

The CAF rats gain most weight (CTRL: +111 ± 40 g; FFD: +211 ± 77 g; CAF: 316 ± 87 g). CAF feeding produced a classical metabolic syndrome-like profile with severe obesity, insulin resistance, dyslipidemia, and liver steatosis, whereas the FFD model led to moderate obesity with preserved insulin sensitivity but elevated blood pressure and hepatic cholesterol accumulation. Thus, the CAF group developed a severe metabolic syndrome-like pathology assessed as continuous metabolic syndrome z-core (CTRL: -2.3 ± 1.0; FFD: -0.4 ± 1.9; CAF: 3.0 ± 2.4). Despite these differences, both diets promoted neuroinflammation and social deficits, likely mediated through gut microbiota-derived metabolites such as 5-HIAA and indoxyl sulfate.

In female rats, self-selected CAF diet drives more severe and distinct pattern of metabolic syndrome-like pathology than a fixed FFD.