Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars

Abstract

The heavy impact of obesity on both the population general health and the economy makes clarifying the underlying mechanisms, identifying pharmacological targets, and developing efficient therapies for obesity of high importance. The main struggle facing obesity research is that the underlying mechanistic pathways are yet to be fully revealed. This limits both our understanding of pathogenesis and therapeutic progress toward treating the obesity epidemic. The current anti-obesity approaches are mainly a controlled diet and exercise which could have limitations. For instance, the “classical” anti-obesity approach of exercise might not be practical for patients suffering from disabilities that prevent them from routine exercise. Therefore, therapeutic alternatives are urgently required. Within this context, pharmacological agents could be relatively efficient in association to an adequate diet that remains the most efficient approach in such situation. Herein, we put a spotlight on potential therapeutic targets for obesity identified following differential genes expression-based studies aiming to find genes that are differentially expressed under diverse conditions depending on physical activity and diet (mainly high-fat), two key factors influencing obesity development and prognosis. Such functional genomics approaches contribute to elucidate the molecular mechanisms that both control obesity development and switch the genetic, biochemical, and metabolic pathways toward a specific energy balance phenotype. It is important to clarify that by “gene-related pathways”, we refer to genes, the corresponding proteins and their potential receptors, the enzymes and molecules within both the cells in the intercellular space, that are related to the activation, the regulation, or the inactivation of the gene or its corresponding protein or pathways. We believe that this emerging area of functional genomics-related exploration will not only lead to novel mechanisms but also new applications and implications along with a new generation of treatments for obesity and the related metabolic disorders especially with the modern advances in pharmacological drug targeting and functional genomics techniques.

Secreted Protein Acidic and Rich in Cysteine as A Regeneration Factor: Beyond the Tissue Repair

“…Therefore, SPARC expression or levels increase following injuries such as myocardial injury [ 23 ], myopathies [ 24 ] and in situations (either physiological or pathological) where tissues undergo changes (repair, renewal and remodeling) such as during obesity [ 18 , 25 ], skeletal muscle regeneration [ 26 ], cancer [ 27 ], systemic sclerosis, hepatic fibrosis [ 28 ] and physical exercise. Indeed, SPARC/ Sparc expression increases in the skeletal muscle during training [ 29 ], as well as following electrical pulse stimulation in muscle cells (considered to be the in vitro equivalent of exercise) [ 30 ]. Such situations do represent a disturbance of the homeostasis that leads to a “negative” regeneration environment.…”

Trefoil Factor Family Member 2 (TFF2) as an Inflammatory-Induced and Anti-Inflammatory Tissue Repair Factor

“…Within the context of diet, it is also worth mentioning that a diet rich in antioxidants would have a beneficial effect on inflammation development [48]. Moreover, the high-fat diet-induced Tff2 gene expression could be related to counteracting inflammation damages, since high-fat diet induces oxidative stress [49] and is usually associated with obesity [50,51] which has both oxidative stress [52] and inflammation [53,54] in its context.…”

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

“…Functional genomics have been proved as a strong tool to characterize many genes specifically induced by different conditions including those related to obesity and within the context of diet and exercise [ 48 , 49 , 50 ]. For instance, we have identified hundreds of genes modulated after HF or LF meals using the serial analysis of gene expression (SAGE) method [ 44 , 45 , 46 , 47 ].…”