Integrated Immunomodulatory Mechanisms through which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction

Abstract

Obesity is a global health concern with rising prevalence that increases the risk of developing other chronic diseases. A causal link connecting overnutrition, the development of obesity and obesity-associated co-morbidities is visceral adipose tissue (AT) dysfunction, characterized by changes in the cellularity of various immune cell populations, altered production of inflammatory adipokines that sustain a chronic state of low-grade inflammation and, ultimately, dysregulated AT metabolic function. Therefore, dietary intervention strategies aimed to halt the progression of obese AT dysfunction through any of the aforementioned processes represent an important active area of research. In this connection, fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to attenuate obese AT dysfunction through multiple mechanisms, ultimately affecting AT immune cellularity and function, adipokine production, and metabolic signaling pathways, all of which will be discussed herein.

Transgenic conversion of ω-6 to ω-3 polyunsaturated fatty acids via fat-1 reduces the severity of post-traumatic osteoarthritis

“…Moreover, serum ω-6 FAs were positively associated with knee synovitis in humans [30]. Growing evidence suggests that dietary FAs can significantly influence circulating levels of various cytokines and adipokines associated with obesity and metabolic syndrome [11][12][13]. Collectively, our findings provide further evidence that ω-6 FAs play a role as proinflammatory mediators, whereas ω-3 FAs may act in an anti-inflammatory manner in obesity and obesityassociated OA.…”

“…Furthermore, these same cytokines are also upregulated following joint injury and with PTOA [7][8][9][10]. In humans, switching to an ω-3 FA-rich diet reduces the serum levels of IL-1β and TNF-α, and increasing evidence suggests that dietary supplementation with ω-3 polyunsaturated fatty acids (PUFAs) can ameliorate metabolic syndrome and modulate circulating levels of leptin and adiponectin [11][12][13]. These data provide the rationale for this study aimed at genetically altering the ratio of ω-6 FAs to ω-3 FAs via an ω-3 FA desaturase in the context of a PTOA model system.…”

Multiple Effekte von Omega-3-Fettsäuren im Fettgewebe

“…Die metabolischen Konkurrenzbeziehungen zwischen Omega-3-Fettsäuren und Omega-6-Fettsäuren sind damit verbunden, [10,12,18].…”

“…Omega-3-Fettsäuren stellen "Gegenspieler" der Effektormoleküle von NF-kappaB (engl: Nuclear factor-kappa B) dar, eines Transkriptionsfaktors für die koordinierte Expression zahlreicher Gene innerhalb der Ausbildung entzündlicher Prozesse. Die Aktivierung von NF-kappaB wird dadurch herabgesetzt, dass langkettige Omega-3-Fettsäuren und viele ihrer Metaboliten der Phosphorylierung eines Inhibitormoleküls entgegenwirken, sodass die Expression "inflammatorischer" Zielgene gehemmt bleibt [2,10]. Diese Wirkung trägt zur Hemmung einer sich bei Adipositas entwickelnden chronisch-subklinischen Entzündung bei.…”

“…Zwischen Fettgewebe-Dysfunktionen bei Adipositas, sich entwickelnden inflammatorischen Prozessen und Folgeerkrankungen, einschließlich Insulinresistenz, bestehen zahlreiche Assoziationen [8,9]. Auf verschiedenen Ebenen wirken Omega-3-Fettsäuren diesen Veränderungen entgegen [10][11][12]. Hieraus ergibt sich, dass ernährungsphysiologische Fragestellungen präventivmedizinisch bedeutsam sind; die langkettigen Omega-3-Fettsäuren EPA und DHA besitzen einen hohen Stellenwert [13,14].…”