title: Integrated analysis of chronic lipotoxicity on muscle metabolism and stress and its reversal by antioxidants.
abstract: Apart from elevated glucose, triglyceride and cholesterol, elevated levels of serum free-fatty acid (FFA) are observed in diabetic patients. Increased FFA load can cause multiple dysregulation which are collectively known as lipotoxicity. Impacts of FFA induced lipotoxicity were evaluated on various cellular responses of metabolism and stress in skeletal muscle myotubes. Under lipotoxicity, oxidative capacity of C2C12 myotubes was reduced and decreased levels ATP and NAD were observed. Lipotoxicity augmented non-oxidative disposal of metabolites in terms of lactate release, IMTG and ceramide synthesis. Concomitantly, insulin resistance was also observed. These impacts were in conjunction with increased cellular stress, inflammation, proteolysis and apoptosis. Quenching of lipotoxicity mediated oxidative stress by antioxidant reverted its deleterious impacts and restored insulin stimulated glucose uptake. In conclusion, the in vitro lipotoxicity makes a system which resembles in vivo pathology of muscle as seen in diabetic patients and represents an integrated perspective of lipotoxicity on various parameters of metabolism and stress.
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Mahesh Kumar
authors.initials: MK
authors.lastname: Verma
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Aggunda Nagaraju
authors.initials: AN
authors.lastname: Yateesh
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Rachapalli
authors.initials: R
authors.lastname: Smitha
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Korrapati
authors.initials: K
authors.lastname: Neelima
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Puttrevana M
authors.initials: PM
authors.lastname: Pallavi
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Madhusudhan
authors.initials: M
authors.lastname: Reddy
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Jayaram
authors.initials: J
authors.lastname: Poornima
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Anup M
authors.initials: AM
authors.lastname: Oommen
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Madanahalli R
authors.initials: MR
authors.lastname: Jagannath
authors.affiliation: Connexios Life Sciences Private Ltd, No. 49, First Main road, 3rd phase, JP Nagar, Bangalore, 560 078 India.
authors.forename: Baggavalli P
authors.initials: BP
authors.lastname: Somesh
keywords: Antioxidant; C2C12 myotubes; Cellular stress; Glucose and fat metabolism; Lipotoxicity; Oxidative capacity