Swimming intervention alleviates insulin resistance and chronic inflammation in metabolic syndrome

Dysregulations of key signaling pathways leading to metabolic syndrome (MetS) are complex eventually leading to cardiovascular events and type 2 diabetes. Dyslipidemia induces progression of insulin resistance and provokes release of proinflammatory cytokines resulting in chronic inflammation, acceleration of lipid peroxidation with further development of atherosclerotic alterations and diabetes. We have proposed a novel combinatorial approach using FDA approved compounds targeting IL-17a and DPP4 to ameliorate a significant portion of the clustered clinical risks in patients with MetS. As MetS is considered a multifactorial disorder, the treatment measures cannot be focused on the specific pathway because other metabolic changes keep the pathological processes in progression. In our present research we have modeled an outcomes of metabolic syndrome treatment using two distinct drug classes. Targets were chosen based on the clustered clinical risks in MetS; dyslipidemia, insulin resistance, impaired glucose control, and chronic inflammation. The AI/ML platform, BIOiSIM, was used in narrowing down two different drug classes with distinct mode of action and modalities. Preliminary studies demonstrated that the most promising drugs belong to DPP-4 inhibitors and IL-17A inhibitors. Alogliptin was chosen to be a candidate for regulating glucose control with long term collateral benefit of weight loss and improved lipid profiles. Secukinumab, IL-17A sequestering agent used in treating psoriasis, was selected as a candidate to address inflammatory disorders. Our analysis suggests this novel combinatorial approach has a high likelihood of ameliorating a significant portion of the clustered clinical risk in MetS.

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Presence and Implications of Sarcopenia in Non-Alcoholic Steatohepatitis

Metabolites ◽

10.3390/metabo11040242 ◽

2021 ◽

Vol 11 (4) ◽

pp. 242

Author(s):

Gregory Habig ◽

Christa Smaltz ◽

Dina Halegoua-DeMarzio

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Muscle Strength ◽

Natural History ◽

Chronic Inflammation ◽

Poor Prognosis ◽

Alcoholic Steatohepatitis ◽

History Of ◽

Underlying Mechanisms ◽

Underlying Pathophysiology

Sarcopenia, defined as the loss of muscle strength, mass, and functionality, confers a poor prognosis in the setting of cirrhosis. Given its clinical significance, a better understanding of the underlying mechanisms leading to cirrhosis, sarcopenia, and their co-occurrence may improve these patients’ outcomes. Non-alcoholic steatohepatitis (NASH) shares many of the same etiologies as sarcopenia, including insulin resistance, chronic inflammation, and ectopic adipocyte deposition, which are hallmarks of metabolic syndrome (MS). NASH thus serves as a prime candidate for further exploration into the underlying pathophysiology and relationship between these three conditions. In this review, we discuss the natural history of NASH and sarcopenia, explore the interplay between these conditions in the scope of MS, and seek to better define how an assessment of muscle mass, strength, and functionality in this population is key to improved diagnosis and management of patients with sarcopenia and NASH.

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