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High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes
Open accessAbstract
Introduction Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids (FFA) present in a high-fat diet on IGF-1 function in cartilage and the role of endoplasmic reticulum (ER) stress.Methods C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan (PG) synthesis. Cultured human chondrocytes were treated with 500 μM FFA palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and PG synthesis. Human chondrocytes were pre-treated with palmitate or 1 mM 4-phenyl butyric acid (PBA) or 1 μM C-Jun N terminal Kinase (JNK) inhibitor, and IGF-1 function (PG synthesis and signaling) was measured.Results Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated PG synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1 function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling.Conclusions Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the mitogen-activated protein (MAP) kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes.
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Diets high in fats, particularly excessive intake of saturated fatty acids, are closely linked to several core symptoms of metabolic syndrome.
“Furthermore, diets high in fats, particularly excessive intake of saturated fatty acids, are closely linked to several core symptoms of metabolic syndrome [11].”
From Impact of Dietary Patterns on Metabolic Syndrome in Young Adults: A Cross-Sectional Study (2024) · cites this paper as [11]
The Introduction says saturated fatty acids play a role in metabolic syndrome and obesity and links palmitate to type 2 diabetes and insulin resistance. It does not establish that high-fat diets or excessive saturated-fat intake are closely linked to several core symptoms of metabolic syndrome; the diet experiment reported in Results concerns cartilage proteoglycan synthesis. (LLM, conf=0.82)
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Impact of Dietary Patterns on Metabolic Syndrome in Young Adults: A Cross-Sectional Study
Liu, J., Lu, W., Lv, Q., Wang, Y., Xu, X., He, Y., Chang, H., Zhao, Y., Zhang, X., Zang, X., et al. (2024) · Nutrients · doi:10.3390/nu16172890 · Cited by 18
“Furthermore, diets high in fats, particularly excessive intake of saturated fatty acids, are closely linked to several core symptoms of metabolic syndrome [11].”
Background
Metadata
- Authors
- Nazli, S. A., Loeser, R. F., Chubinskaya, S., Willey, J. S., & Yammani, R. R.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of North Carolina at Chapel Hill (US)
- Rush University (US)
- Corresponding author
- Yammani, R.R.
- Venue
- Osteoarthritis and Cartilage
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 25
- Issue
- 9
- Pages
- 1516-1521
- ISSN
- 1063-4584 (ISSN-L)
- PMC
- PMC5565687
- OpenAlex
- W2618317121
- Cited by
- 43
- References
- 25
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 1
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Osteoarthritis and Cartilage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis, Musculoskeletal and Skin Diseases (R01 AR066105, R21 AR 063835)
- National Institute on Aging (R01 AG044034)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin-like growth factor I, chondrocytes, high-fat diet, palmitate, saturated fatty acids, endoplasmic reticulum stress, proteoglycan synthesis, cartilage, JNK, CHOP, 4-phenylbutyric acid, osteoarthritis, free fatty acids
- MeSH terms
- Animals, Cartilage, Articular, Humans, Insulin-Like Growth Factor I, Male, Mice, Inbred C57BL, Phosphorylation, Proteoglycans, Oleic Acid, Palmitic Acid, Chondrocytes, MAP Kinase Signaling System, Diet, High-Fat, Endoplasmic Reticulum Stress
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