Dietary saturated fatty acid palmitate promotes cartilage lesions and activates the unfolded protein response pathway in mouse knee joints
Open Access
- 22 February 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (2), e0247237
- https://doi.org/10.1371/journal.pone.0247237
Abstract
Increased intake of dietary saturated fatty acids has been linked to obesity and the development of Osteoarthritis (OA). However, the mechanism by which these fats promote cartilage degradation and the development of OA is not clearly understood. Here, we report the effects of consumption of common dietary saturated and unsaturated fatty acids, palmitate and oleate, respectively, on body weight, metabolic factors, and knee articular cartilage in a mouse model of diet-induced obesity. Mice fed on a diet rich in saturated or unsaturated fatty acid gained an equal amount of weight; however, mice fed a palmitate diet, but not a control or oleate diet, exhibited more cartilage lesions and increased expression of 1) unfolded protein response (UPR)/endoplasmic reticulum (ER) stress markers including BIP, P-IRE1 alpha, XBP1, ATF4, and CHOP; 2) apoptosis markers CC3 and C-PARP; and 3) negative cell survival regulators Nupr1 and TRB3, in knee articular cartilage. Palmitate-induced apoptosis was confirmed by TUNEL staining. Likewise, dietary palmitate was also increased the circulatory levels of classic proinflammatory cytokines, including IL-6 and TNF-alpha. Taken together, our results demonstrate that increased weight gain is not sufficient for the development of obesity-linked OA and suggest that dietary palmitate promotes UPR/ER stress and cartilage lesions in mouse knee joints. This study validates our previous in vitro findings and suggests that ER stress could be the critical metabolic factor contributing to the development of diet/obesity induced OA.Funding Information
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR066105)
This publication has 51 references indexed in Scilit:
- Osteoarthritis, inflammation and obesityCurrent Opinion in Rheumatology, 2013
- Osteoarthritis: A disease of the joint as an organArthritis & Rheumatism, 2012
- Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammationPathobiology of Aging & Age-related Diseases, 2012
- Obesity and Free Fatty AcidsEndocrinology and Metabolism Clinics of North America, 2008
- Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part IIArthritis & Rheumatism, 2007
- Obesity and Diabetes in the Developing World — A Growing ChallengeThe New England Journal of Medicine, 2007
- Projections of US prevalence of arthritis and associated activity limitationsArthritis & Rheumatism, 2005
- The Role of Cytokines in Cartilage Matrix Degeneration in OsteoarthritisClinical Orthopaedics and Related Research, 2004
- Osteoarthritis: New Insights. Part 1: The Disease and Its Risk FactorsAnnals of Internal Medicine, 2000
- Body Weight, Body Mass Index, and Incident Symptomatic Osteoarthritis of the Hand, Hip, and KneeEpidemiology, 1999