Blueberry Consumption Challenges Hepatic Mitochondrial Bioenergetics and Elicits Transcriptomics Reprogramming in Healthy Wistar Rats

Abstract

An emergent trend of blueberries’ (BB) “prophylactic” consumption, due to their phytochemicals’ richness and well-known health-promoting claims, is widely scaled-up. However, the benefits arising from BB indiscriminate intake remains puzzling based on incongruent preclinical and human data. To provide a more in-depth elucidation and support towards a healthier and safer consumption, we conducted a translation-minded experimental study in healthy Wistar rats that consumed BB in a juice form (25 g/kg body weight (BW)/day; 14 weeks’ protocol). Particular attention was paid to the physiological adaptations succeeding in the gut and liver tissues regarding the acknowledged BB-induced metabolic benefits. Systemically, BB boosted serum antioxidant activity and repressed the circulating levels of 3-hydroxybutyrate (3-HB) ketone bodies and 3-HB/acetoacetate ratio. Moreover, BB elicited increased fecal succinic acid levels without major changes on gut microbiota (GM) composition and gut ultra-structural organization. Remarkably, an accentuated hepatic mitochondrial bioenergetic challenge, ensuing metabolic transcriptomic reprogramming along with a concerted anti-inflammatory pre-conditioning, was clearly detected upon long-term consumption of BB phytochemicals. Altogether, the results disclosed herein portray a quiescent mitochondrial-related metabolomics and hint for a unified adaptive response to this nutritional challenge. The beneficial or noxious consequences arising from this dietary trend should be carefully interpreted and necessarily claims future research.

Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression

“…Moreover, other studies showed an antioxidant effect of bilberry leaves extract in serum of male Wistar rats under a double challenge composed of HFD and STZ [ 93 ]. Likewise, in a recent study from our group, long-term supplementation of BB juice boosted serum antioxidant activity in a healthy Wistar rats [ 130 ]. Nevertheless, there has been some controversy on BB-derived polyphenols benefits on total antioxidant activity in both in vivo and human studies [ 131 , 132 , 133 , 134 , 135 ].…”

“…In fact, this polyphenol has a positive impact on mitochondrial biogenesis related with an increased mRNA expression of PGC-1α and SIRT1 along with higher contents of mtDNA and cytochrome c [ 150 ]. Remarkably, recent data from our group revealed that long-term BB fruits intake in a juice form elicited an accentuated bioenergetic remodeling in isolated hepatic mitochondria along with a metabolic transcriptional adaptive response in healthy animals [ 130 ]. Further animal research also showed that the attenuation of hepatic steatosis and enhancement of lipolysis following exposure of hepatic cells to BB polyphenols can be promoted by modulation of autophagy [ 36 ].…”

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics

“…BBs juice (BJ) was obtained as described in a previous study [38]. Briefly, BBs were weighed, blended with sucrose solution (35%), and converted into juice to assure consumption of whole fruit parts (peel, pulp, and seeds).…”

“…The volume of sucrose solution added was corrected every day to guarantee that 25 g/kg of BW of BBs were daily consumed by the animals. This BBs dose was selected based on a previous study of our group [38].…”

“…Recently, our group underscored that long-term BBs supplementation in a healthy condition triggered an expressive polyphenol-derived remodeling of hepatic mitochondrial bioenergetics [38]. Given the well-recognized hepatic mitochondrial impairments in overt T2DM, we hypothesized that BBs' ability to counteract prediabetes would follow similar traits.…”