Microencapsulated fermented wild blueberries attenuate diet-induced lipid dysmetabolism

Dietary interventions, such as anthocyanins of wild blueberries, offer safer alternatives for the management of metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). A novel process has been developed by using fermentation to enhance the bioactive diversity and efficacy, while microencapsulation improves their stability. Wild blueberries were sequentially fermented with Saccharomyces cerevisiae and Komagataeibacter spp., then microencapsulated with inulin and maltodextrin (1:1 w/w) by spray drying. Male C57BL/6J mice on a high-fat, high-sucrose diet received fermented, non-fermented, or microencapsulated fermented wild blueberries (416 mg gallic acid equivalents/kg body weight/day) for 22 weeks. Controls included chow-fed and high-fat, high-sucrose-fed non-supplemented groups. Microencapsulated fermented wild blueberries reduced food and energy intake, body weight gain, total body fat, liver weight, hepatic lipid accumulation, plasma total and free cholesterol, and hepatic triglycerides and preserved normal liver structure in high-fat, high-sucrose diet-fed mice. Western blots revealed that this encapsulated supplement upregulated hepatic phosphorylated adenosine monophosphate (AMP)-activated protein kinase-alpha ((p-AMPK)/AMPK ratio), reduced total acetyl-CoA carboxylase, fatty acid synthase, and cluster of differentiation 36 (CD36) protein levels, indicating suppressed lipogenesis and fatty acid uptake. Also, the supplement restored gut microbiota alpha diversity altered by the high-calorie diet and enriched beneficial species such as Akkermansia in the gut. Thus, this novel process can be utilized to develop a functional food ingredient or nutraceutical with potential applications in the prevention of MASLD among at-risk individuals, as well as serving as an adjunct therapeutic strategy for patients with established metabolic syndrome.