Carnosic Acid Attenuates the Free Fatty Acid-Induced Insulin Resistance in Muscle Cells and Adipocytes.

Abstract

Elevated blood free fatty acids (FFAs), as seen in obesity, impair insulin action leading to insulin resistance and Type 2 diabetes mellitus. Several serine/threonine kinases including JNK, mTOR, and p70 S6K cause serine phosphorylation of the insulin receptor substrate (IRS) and have been implicated in insulin resistance. Activation of AMP-activated protein kinase (AMPK) increases glucose uptake, and in recent years, AMPK has been viewed as an important target to counteract insulin resistance. We reported previously that carnosic acid (CA) found in rosemary extract (RE) and RE increased glucose uptake and activated AMPK in muscle cells. In the present study, we examined the effects of CA on palmitate-induced insulin-resistant L6 myotubes and 3T3L1 adipocytes. Exposure of cells to palmitate reduced the insulin-stimulated glucose uptake, GLUT4 transporter levels on the plasma membrane, and Akt activation. Importantly, CA attenuated the deleterious effect of palmitate and restored the insulin-stimulated glucose uptake, the activation of Akt, and GLUT4 levels. Additionally, CA markedly attenuated the palmitate-induced phosphorylation/activation of JNK, mTOR, and p70S6K and activated AMPK. Our data indicate that CA has the potential to counteract the palmitate-induced muscle and fat cell insulin resistance.

• Authors: Danja J Den Hartogh, Filip Vlavcheski, Adria Giacca, Rebecca E K MacPherson, Evangelia Tsiani
• Journal: Cells (Cells) Vol. 11 Issue 1 (01 05 2022) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 35011728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abietanes
• Fatty Acids, Nonesterified
• Insulin
• Insulin Receptor Substrate Proteins
• Palmitates
• Phosphoserine
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases
• AMP-Activated Protein Kinases
• Glucose
• salvin

Topics

• 3T3-L1 Cells
• AMP-Activated Protein Kinases (metabolism)
• Abietanes (pharmacology)
• Adipocytes (drug effects, pathology)
• Animals
• Cell Line
• Fatty Acids, Nonesterified (toxicity)
• Glucose (metabolism)
• Insulin (pharmacology)
• Insulin Receptor Substrate Proteins (metabolism)
• Insulin Resistance
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Models, Biological
• Muscle Cells (drug effects, pathology)
• Muscle Fibers, Skeletal (drug effects, metabolism)
• Palmitates (toxicity)
• Phosphorylation (drug effects)
• Phosphoserine (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• TOR Serine-Threonine Kinases (metabolism)