The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects
Open accessAbstract
Summary Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16–18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g. palmitic-acid-9-hydroxy-stearic acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR-120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
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“The major pathogenic factors underlying T2D are resistance to insulin action in peripheral tissues and dysregulated insulin secretion.”
BackgroundInfluentialBenhamed, F., Denechaud, P.-D., Lemoine, M., Robichon, C., Moldes, M., Bertrand-Michel, J., Ratziu, V., Serfaty, L., Housset, C., Capeau, J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci41636 · Cited by 408 · cited 1×
“Similarly, an increased ratio of monounsaturated to saturated fatty acids in the liver is associated with insulin sensitivity even with extensive hepatic steatosis (Benhamed et al., 2012).”
Background
Cited by
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Samuel, V. T., & Shulman, G. I. (2016) · Journal of Clinical Investigation · doi:10.1172/jci77812 · Cited by 1,484
Adipogenesis and metabolic health
Ghaben, A. L., & Scherer, P. E. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0093-z · Cited by 1,395
Insulin action and resistance in obesity and type 2 diabetes
Czech, M. P. (2017) · Nature Medicine · doi:10.1038/nm.4350 · Cited by 1,258
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Identification of bioactive metabolites using activity metabolomics
Rinschen, M. M., Ivanisevic, J., Giera, M., & Siuzdak, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0108-4 · Cited by 1,008
Metadata
- Authors
- Yore, M. M., Syed, I., Moraes-Vieira, P. M., Zhang, T., Herman, M. A., Homan, E. A., Patel, R. T., Lee, J., Chen, S., Peroni, O. D., Dhaneshwar, A. S., Hammarstedt, A., Smith, U., McGraw, T. E., Saghatelian, A., & Kahn, B. B.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 159
- Issue
- 2
- Pages
- 318-332
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2152560090
- Cited by
- 842
- References
- 7
- FWCI
- 20.68
- Type
- journal article
- Language
- en
- Open access
- bronze
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