Saturated fatty acids promote chondrocyte matrix remodeling through reprogramming of autophagy pathways

Sunderajhan Sekar; Xiaoxin Wu; Thor Friis; Ross Crawford; Indira Prasadam; Yin Xiao

doi:10.1016/j.nut.2018.02.018

Saturated fatty acids promote chondrocyte matrix remodeling through reprogramming of autophagy pathways

Nutrition. 2018 Oct:54:144-152. doi: 10.1016/j.nut.2018.02.018. Epub 2018 Mar 20.

Authors

Sunderajhan Sekar¹, Xiaoxin Wu², Thor Friis¹, Ross Crawford³, Indira Prasadam⁴, Yin Xiao¹

Affiliations

¹ Institute of Health and Biomedical Innovation, School of Chemistry, Physics, Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland, Australia.
² Institute of Health and Biomedical Innovation, School of Chemistry, Physics, Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, China.
³ Institute of Health and Biomedical Innovation, School of Chemistry, Physics, Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland, Australia; The Prince Charles Hospital, Orthopedic Department, Brisbane, Queensland, Australia.
⁴ Institute of Health and Biomedical Innovation, School of Chemistry, Physics, Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: I.prasadam@qut.edu.au.

PMID: 29852453
DOI: 10.1016/j.nut.2018.02.018

Abstract

Objectives: Obesity is a known strong risk factor for the onset of knee osteoarthritis and is often accompanied by dysregulated lipid metabolism with elevated levels of free fatty acids such as saturated fatty acids (SFAs). The purpose of this study was to determine how autophagy varies in chondrocytes in response to predominant SFAs such as lauric, myristic, palmitic, and stearic acids.

Methods: Normal human articular cartilage chondrocytes and C28/I2 chondrocyte cell lines were stimulated with different SFAs in both the absence and presence of interleukin-1β to study the effects of SFA and inflammatory cytokines in mediating the activation of autophagy. The effects of rapamycin and LY290042 on autophagy in response to different SFAs were also assessed.

Results: Palmitic and stearic acid stimulation of chondrocytes resulted in increased activation of both autophagy and the canonical NFκB pathway as evidenced by increased expressions of the key autophagy markers microtubule-associated protein-1 light chain 3, autophagy-related 5, beclin-1, and NFκB p65. In contrast, lauric acid stimulation resulted in decreased autophagy activation as shown by decreased expressions of microtubule-associated protein-1 light chain 3, autophagy-related 5, and beclin-1, which suggests decreased cellular stress.

Conclusions: These results represent a novel mechanism by which various SFAs activate autophagy and simultaneously modulate NFκB signaling pathways and the expression of chondrocyte regulatory genes.

Keywords: Autophagy; NFκB pathway; Obesity; Osteoarthritis; Saturated fatty acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / drug effects*
Cartilage, Articular / cytology
Cell Line
Chondrocytes / metabolism*
Extracellular Matrix / metabolism*
Fatty Acids / pharmacology*
Humans
NF-kappa B / metabolism
Signal Transduction / drug effects*

Substances

Fatty Acids
NF-kappa B