Modulation of Insulin Resistance and the Adipocyte-Skeletal Muscle Cell Cross-Talk by LCn-3PUFA

Abstract

The cross-talk between skeletal muscle and adipose tissue is involved in the development of insulin resistance (IR) in skeletal muscle, leading to the decrease in the anabolic effect of insulin. We investigated if the long chain polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and docosapentaenoic acids (EPA and DPA, respectively) could (1) regulate the development of IR in 3T3-L1 adipocytes and C2C12 muscle cells and (2) inhibit IR in muscle cells exposed to conditioned media (CM) from insulin-resistant adipocytes. Chronic insulin (CI) treatment of adipocytes and palmitic acid (PAL) exposure of myotubes were used to induce IR in the presence, or not, of LCn-3PUFA. EPA (50 µM) and DPA (10 µM) improved PAL-induced IR in myotubes, but had only a partial effect in adipocytes. CM from adipocytes exposed to CI induced IR in C2C12 myotubes. Although DPA increased the mRNA levels of genes involved in fatty acid (FA) beta-oxidation and insulin signaling in adipocytes, it was not sufficient to reduce the secretion of inflammatory cytokines and prevent the induction of IR in myotubes exposed to adipocyte’s CM. Treatment with DPA was able to increase the release of adiponectin by adipocytes into CM. In conclusion, DPA is able to protect myotubes from PAL-induced IR, but not from IR induced by CM from adipocytes.

PPARG Hypermethylation as the First Epigenetic Modification in Newly Onset Insulin Resistance in Human Adipocytes

“…We demonstrated that DNA methylation is an essential component of IR pathogenesis in adipose tissue. The IR was induced in experimental cells: 3T3-L1 adipocytes and human adipocytes collected from SAT and VAT by palmitic acid, which is one of the most common methods used by numerous researchers [22,23]. We successfully induced IR both in 3T3-L1 and human adipocytes, which was confirmed by a glucose uptake assay.…”

Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes

“…An in vitro model of palmitate-induced insulin resistant 3T3-L1 adipocytes has been established to study obesity-associated complications, including insulin resistance [ 13 , 16 , 23 ]. Indeed, several studies have shown that concentrations of 0.2–0.75 mM palmitate are enough to induce insulin resistance in various cell lines over a 16–24 h period [ 11 , 24 ]. In our laboratory, we have explored metabolic alterations associated with palmitate-induced insulin resistance in 3T3-L1 adipocytes.…”

Phospholipid Derivatives of Cinnamic Acid Restore Insulin Sensitivity in Insulin Resistance in 3T3-L1 Adipocytes

“…We evaluated them on the 3T3-L1 adipocytes, the most commonly studied cell model used as the adipose tissue model in cell culture to examine various types of metabolic disorders [ 33 , 34 ]. It responds to insulin similar to human adipocytes; as well, there are the same methods to induce resistance to insulin using the same chemical components [ 35 , 36 ]. Therefore, in the present study, we used palmitic acid to induce insulin resistance in mature 3T3-L1 adipocytes, which successfully developed resistance to insulin in experimental cells, proven by the insulin-stimulated glucose uptake measurements.…”