Cranberry Proanthocyanidins as a Therapeutic Strategy to Curb Metabolic Syndrome and Fatty Liver-Associated Disorders.
Francis FeldmanMireille KoudoufioRamy El-JalboutMathilde Foisy SauvéLena AhmaraniAlain Théophile SanéNour-El-Houda Ould-ChikhThierry N'TimbaneNatalie PateyYves DesjardinsAlain StintziSchohraya SpahisEmile LevyPublished in: Antioxidants (Basel, Switzerland) (2022)
While the prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, no optimal pharmacotherapy is readily available to address its multifaceted risk factors and halt its complications. This growing challenge mandates the development of other future curative directions. The purpose of the present study is to investigate the efficacy of cranberry proanthocyanidins (PACs) in improving MetS pathological conditions and liver complications; C57BL/6J mice were fed either a standard chow or a high fat/high sucrose (HFHS) diet with and without PACs (200 mg/kg), delivered by daily gavage for 12 weeks. Our results show that PACs lowered HFHS-induced obesity, insulin resistance, and hyperlipidemia. In conjunction, PACs lessened circulatory markers of oxidative stress (OxS) and inflammation. Similarly, the anti-oxidative and anti-inflammatory capacities of PACs were noted in the liver in association with improved hepatic steatosis. Inhibition of lipogenesis and stimulation of beta-oxidation could account for PACs-mediated decline of fatty liver as evidenced not only by the expression of rate-limiting enzymes but also by the status of AMPKα (the key sensor of cellular energy) and the powerful transcription factors (PPARα, PGC1α, SREBP1c, ChREBP). Likewise, treatment with PACs resulted in the downregulation of critical enzymes of liver gluconeogenesis, a process contributing to increased rates of glucose production in type 2 diabetes. Our findings demonstrate that PACs prevented obesity and improved insulin resistance likely via suppression of OxS and inflammation while diminishing hyperlipidemia and fatty liver disease, as clear evidence for their strength of fighting the cluster of MetS abnormalities.
Keyphrases
- insulin resistance
- high fat diet induced
- metabolic syndrome
- type diabetes
- skeletal muscle
- high fat diet
- risk factors
- oxidative stress
- adipose tissue
- polycystic ovary syndrome
- physical activity
- uric acid
- weight loss
- transcription factor
- diabetic rats
- glycemic control
- dna damage
- nitric oxide
- poor prognosis
- cardiovascular disease
- body mass index
- blood pressure
- cell proliferation
- ischemia reperfusion injury
- current status
- signaling pathway
- endothelial cells
- cardiovascular risk factors
- blood glucose
- drug induced
- preterm birth
- replacement therapy