Journal of Liver

Role of Inflammation in Hepatic Insulin Resistance and Metabolic Dysfunction: Pathophysiological Insights

Marwa Qumosani^* Department of Hepatobiliary and Surgery, Corvinus University of Budapest, Budapest, Hungary
^*Correspondence: Marwa Qumosani, Department of Hepatobiliary and Surgery, Corvinus University of Budapest, Budapest, Hungary, Email:

Received: 01-Mar-2024, Manuscript No. JLR-24- 25406; Editor assigned: 04-Mar-2024, Pre QC No. JLR-24- 25406(PQ); Reviewed: 25-Mar-2024, QC No. JLR-24- 25406; Revised: 01-Apr-2024, Manuscript No. JLR-24- 25406(R); Published: 08-Apr-2024, DOI: 10.35248/2167-0889.24.13.217

Description

Insulin resistance and metabolic dysfunction represent significant health challenges globally, particularly in the context of chronic diseases like Type 2 Diabetes Mellitus (T2DM) and Non-Alcoholic Fatty Liver Disease (NAFLD). Among the various organs involved in glucose and lipid metabolism, the liver plays a central role. Hepatic insulin resistance, characterized by impaired insulin signaling and glucose metabolism in liver cells, is a key contributor to the pathogenesis of T2DM and NAFLD. Recent research has shed explained the interplay between inflammation and hepatic insulin resistance, providing valuable insights into the underlying pathophysiological mechanisms. Inflammation is increasingly recognized as an important player in the development and progression of hepatic insulin resistance. Chronic low-grade inflammation, often observed in obesity and metabolic syndrome, leads to the activation of inflammatory pathways within the liver. This dysregulated signaling cascade contributes to aberrant glucose production and lipid metabolism in the liver, exacerbating insulin resistance and metabolic dysfunction. Several mechanisms underlie the crosstalk between inflammation and hepatic insulin resistance. One pivotal pathway involves the activation of serine kinases, such as IKKβ and Jun N-Terminal Kinase (JNK), within hepatocytes in response to pro-inflammatory stimuli. These kinases phosphorylate Insulin Receptor Substrate (IRS) proteins at serine residues, thereby inhibiting insulin receptor signaling and promoting insulin resistance. Additionally, inflammatory cytokines activate transcription factors like Nuclear Factor-Kappa B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3), which modulate the expression of genes involved in gluconeogenesis, lipogenesis, and inflammation, further exacerbating metabolic dysfunction in the liver.

Moreover, emerging evidence suggests a important role for adipose tissue-derived factors, known as adipokines, in linking inflammation to hepatic insulin resistance. Adipokines like adiponectin, leptin, and resistin exert pleiotropic effects on hepatic insulin sensitivity and inflammation. While adiponectin exhibits anti-inflammatory and insulin-sensitizing properties, leptin and resistin promote inflammation and insulin resistance in the liver through diverse signaling pathways, including AMP-Activated Protein Kinase (AMPK) and Mammalian Target of Rapamycin (mTOR). Furthermore, gut-derived factors, particularly microbial products and metabolites, contribute to the inflammatory milieu in the liver and plays an important role in the pathogenesis of hepatic insulin resistance. Dysbiosis of the gut microbiota, characterized by alterations in microbial composition and function, is associated with increased intestinal permeability and systemic inflammation, which can exacerbate hepatic insulin resistance and metabolic dysfunction. Short-Chain Fatty Acids (SCFAs), produced by bacterial fermentation of dietary fibers, exert beneficial effects on insulin sensitivity by modulating immune responses and inflammation in the liver. Understanding the intricate interplay between inflammation and hepatic insulin resistance offers a potential avenue for therapeutic intervention. Targeting inflammatory pathways and key mediators, such as cytokines and kinases, holds potential for mitigating insulin resistance and improving metabolic health in individuals with T2DM and NAFLD. Anti-inflammatory agents, including Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), corticosteroids, and inhibitors of pro-inflammatory cytokines, are being explored as adjunctive therapies to complement lifestyle interventions and pharmacological agents targeting insulin resistance.

Conclusion

Moreover, lifestyle modifications, including dietary interventions and regular exercise, can attenuate inflammation and enhance hepatic insulin sensitivity, thereby reducing the risk of metabolic disorders. Dietary strategies focused on reducing intake of refined carbohydrates, saturated fats, and processed foods while increasing consumption of fiber-rich fruits, vegetables, and omega-3 fatty acids have shown in ameliorating hepatic inflammation and insulin resistance. Elucidating the intricate molecular mechanisms underlying this interplay provides valuable insights into potential therapeutic targets for managing insulin resistance-related disorders. Further research is warranted to explore novel strategies aimed at modulating inflammation and restoring metabolic homeostasis in individuals at risk of T2DM and NAFLD. By addressing inflammation-driven pathways, clinicians and researchers can pave the way for more effective management and prevention of insulin resistance-related complications, thereby improving the overall health outcomes of affected individuals.