Dietary saturated fatty acid palmitate promotes cartilage lesions and activates the unfolded protein response pathway in mouse knee joints

Li Tan, Lindsey R. Harper, Alexandra Armstrong, Cathy S. Carlson, Raghunatha R. Yammani

Research output: Contribution to journalArticlepeer-review


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-IRE1α, 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-α. 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.

Original languageEnglish (US)
Article numbere0247237
JournalPloS one
Issue number2 February
StatePublished - Feb 2021

Bibliographical note

Publisher Copyright:
Copyright: © 2021 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Animals
  • Apoptosis/drug effects
  • Biomarkers/metabolism
  • Cartilage, Articular/drug effects
  • Cell Survival/drug effects
  • Chondrocytes/drug effects
  • Diet/adverse effects
  • Fatty Acids/adverse effects
  • Knee Joint/drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis/chemically induced
  • Palmitates/adverse effects
  • Signal Transduction/drug effects
  • Unfolded Protein Response/drug effects

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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