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Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes.

Miao H, Chen L, Hao L, Zhang X, Chen Y, Ruan Z, Liang H - Sci Rep (2015)

Bottom Line: We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes.Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo.In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

ABSTRACT
The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.

No MeSH data available.


Related in: MedlinePlus

Correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index (BMI) in patients with osteoarthritis.(a) Correlation of plasma lactate levels with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.65, and P < 0.05. (b) Correlation of HIF1α protein levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.80, and P < 0.05. (c) Correlation of IL-6 mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.78, and P < 0.05. (d) Correlation of TNF-α mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.88, and P < 0.05. (e) Correlation of IL-1β mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.87, and P < 0.05. (f) Correlation of VEGF mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.67, and P < 0.05.
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f7: Correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index (BMI) in patients with osteoarthritis.(a) Correlation of plasma lactate levels with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.65, and P < 0.05. (b) Correlation of HIF1α protein levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.80, and P < 0.05. (c) Correlation of IL-6 mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.78, and P < 0.05. (d) Correlation of TNF-α mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.88, and P < 0.05. (e) Correlation of IL-1β mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.87, and P < 0.05. (f) Correlation of VEGF mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.67, and P < 0.05.

Mentions: Aforementioned results revealed that lactate/HIF1α pathway was involved in saturated free fatty acid-induced production of proinflammatory cytokines and VEGF. To further correlate this mechanism to physiological condition, we investigated the levels of plasma lactate, cartilage HIF1α and cytokines in age-matched female human donors with OA. Results revealed that production of plasma lactate (Fig. 7a), cartilage HIF1α (Fig. 7b), IL-6 (Fig. 7c), TNF-α (Fig. 7d), IL-1β (Fig. 7e) and VEGF (Fig. 7f) were positively correlated with the BMI in human donors.


Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes.

Miao H, Chen L, Hao L, Zhang X, Chen Y, Ruan Z, Liang H - Sci Rep (2015)

Correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index (BMI) in patients with osteoarthritis.(a) Correlation of plasma lactate levels with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.65, and P < 0.05. (b) Correlation of HIF1α protein levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.80, and P < 0.05. (c) Correlation of IL-6 mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.78, and P < 0.05. (d) Correlation of TNF-α mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.88, and P < 0.05. (e) Correlation of IL-1β mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.87, and P < 0.05. (f) Correlation of VEGF mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.67, and P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4536527&req=5

f7: Correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index (BMI) in patients with osteoarthritis.(a) Correlation of plasma lactate levels with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.65, and P < 0.05. (b) Correlation of HIF1α protein levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.80, and P < 0.05. (c) Correlation of IL-6 mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.78, and P < 0.05. (d) Correlation of TNF-α mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.88, and P < 0.05. (e) Correlation of IL-1β mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.87, and P < 0.05. (f) Correlation of VEGF mRNA levels in the cartilages with the BMI in human subjects (n = 10). Pearson’s correlations: R = 0.67, and P < 0.05.
Mentions: Aforementioned results revealed that lactate/HIF1α pathway was involved in saturated free fatty acid-induced production of proinflammatory cytokines and VEGF. To further correlate this mechanism to physiological condition, we investigated the levels of plasma lactate, cartilage HIF1α and cytokines in age-matched female human donors with OA. Results revealed that production of plasma lactate (Fig. 7a), cartilage HIF1α (Fig. 7b), IL-6 (Fig. 7c), TNF-α (Fig. 7d), IL-1β (Fig. 7e) and VEGF (Fig. 7f) were positively correlated with the BMI in human donors.

Bottom Line: We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes.Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo.In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

ABSTRACT
The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.

No MeSH data available.


Related in: MedlinePlus