Mechanisms of effects of tart cherry in obesity, inflammation and aging

Obesity is a complex disease, which has become a major health problem worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia, as well as pathologic endocrine alterations of adipose tissue including local and systemic low-grade inflammation. Aging has a significant influence on economy, health and demography with healthy aging being a global challenge. Aging and health span are determined by both environmental and genetic factors. It is evident that obesity reduces cellular and molecular functions and may lead to aging process as well. Additionally, pathological differences during obesity such as inflammation and oxidative stress as well as cellular damage may accelerate the rate of aging. Therefore, there is a close association between aging and obesity. The insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway is a key mediator of aging in C. elegans and mammals. Specifically, DAF-2 signaling, an ortholog of human IGF, controls DAF-16/FOXO transcription factor, a master regulator of metabolism and longevity. Moreover, mitochondrial dysfunction and oxidative stress are both linked to aging. Dietary interventions are among effective non-genetic or pharmacological means to combat both obesity and aging. In this dissertation, we primarily focused on how nutritional interventions can be used to reduce adipose tissue inflammation associated with obesity and aging. Basic and clinical studies demonstrate that foods containing bioactive compounds are capable of preventing both obesity and adipose tissue inflammation, in human subjects and animal models of obesity. Also, some studies have shown potential interactions between obesity and aging such as shortening of telomeres, mitochondrial dysfunction, and cellular senescence, and both obesity and aging share some of the common pathways including IGF-1. Most studies have shown that the consumption of anthocyanin-rich food reduces the development of chronic diseases including metabolic diseases and delay the aging process. Tart cherry (TC) (Prunus cerasus) contains the greatest concentrations of anthocyanin flavonoids among vegetables and fruits, including other cherries. However, many studies have used strawberry, blueberry and sweet cherry anthocyanin or extracts to reduce such disease conditions; and fewer studies have addressed the effects of tart cherry on adipose tissue inflammation, obesity and aging. Hence, our objectives were: 1. Identify the potential anti-inflammatory activities of TC extract rich in anthocyanins in adipose tissue inflammation in obese Zucker fatty rats (OZFR) and cultured 3T3-L1 adipocytes; and 2. Identify lifespan regulating effects of TC in C. elegans. Our results of aim 1 showed TC supplementation reduced adipose tissue inflammation both in OZFR and 3T3-L1 adipocytes part via NFkB pathway which is one of the major inflammatory pathways. Moreover, TC increased antioxidant mechanisms in both animal and cell models. In our C. elegans study in aim 2, we found that TC supplementation increased the mean lifespan of wild type C. elegans mainly via IIS pathway. Furthermore, TC increased the expression of antioxidant genes and spare respiration rate in C. elegans. In conclusion, our findings herein demonstrated that dietary TC supplementation may support metabolically healthy obesity through significantly reduced inflammation in adipose tissue. In addition, our work highlighted the importance of TC in delaying aging and improving mechanism involved in healthy aging.