The Associations of Individual and Subclasses of Nonesterified Fatty Acids With Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study

Overview

Journal J Gerontol A Biol Sci Med Sci

Specialty Geriatrics

Date 2022 Sep 26

PMID 36156076

Authors

Peter D Ahiawodzi

Petra Buzkova

Alice H Lichtenstein

Nirupa R Matthan

Joachim H Ix

Jorge R Kizer

Russell P Tracy

Alice Arnold

Anne B Newman

David Siscovick

Luc Djousse

Kenneth J Mukamal

Affiliations

Soon will be listed here.

Abstract

Background: We sought to determine the associations between individual nonesterified fatty acids (NEFAs) and disability and mobility limitation.

Methods: We studied 1 734 participants in the Cardiovascular Health Study (CHS), an ongoing population-based cohort study of community-living older American adults. We measured 35 individual NEFA species in fasting serum samples obtained at the 1996-1997 clinic visit. Using yearly assessments of activities of daily living and self-reported mobility, we identified participants with incident disability or mobility limitation during 15 years of follow-up. Cox proportional hazards regression models were used to determine the associations between per SD increment in the individual NEFAs and incident disability and mobility limitations with adjustment for potential confounding factors.

Results: Higher concentrations of total and a broad range of individual NEFA species were associated with risk of disability and mobility limitation (disability: HR per SD of total NEFA [SD = 174.70] = 1.11, 95% CI = 1.04-1.18, p = .001; mobility limitation: HR per SD of total NEFA = 1.09, 95% CI = 1.02-1.16, p = .01). Among individual saturated NEFAs (SFAs), myristic (14:0) and palmitic (16:0) acids were significantly associated with higher risk of both disability and mobility limitations, but longer-chain FAs were not. Most individual monounsaturated (MUFA), n-6 polyunsaturated fatty acids (PUFAs), and trans FAs were positively significantly associated with higher risks of both disability and mobility limitation. In contrast, most n-3 PUFA species were not associated with disability or mobility limitation.

Conclusions: Higher risks of disability and mobility limitation were observed for proinflammatory intermediate-chain SFAs, MUFAs, n-6 PUFAs, and trans FAs. Our findings indicated no significant association for anti-inflammatory n-3 PUFAs.

References

Walker M, Matthan N, Goldbaum A, Meng H, Lamon-Fava S, Lakshman S . Dietary patterns influence epicardial adipose tissue fatty acid composition and inflammatory gene expression in the Ossabaw pig. J Nutr Biochem. 2019; 70:138-146. PMC: 6958552. DOI: 10.1016/j.jnutbio.2019.04.013. View

Folch J, Lees M, SLOANE STANLEY G . A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226(1):497-509. View

Liu L, Martin R, Chan C . Palmitate-activated astrocytes via serine palmitoyltransferase increase BACE1 in primary neurons by sphingomyelinases. Neurobiol Aging. 2012; 34(2):540-50. PMC: 3459302. DOI: 10.1016/j.neurobiolaging.2012.05.017. View

Cushman M, Cornell E, Howard P, Bovill E, Tracy R . Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem. 1995; 41(2):264-70. View

Steinberg H, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A . Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest. 1997; 100(5):1230-9. PMC: 508300. DOI: 10.1172/JCI119636. View

Friedman E, Mroczek D, Christ S . Multimorbidity, inflammation, and disability: a longitudinal mediational analysis. Ther Adv Chronic Dis. 2019; 10:2040622318806848. PMC: 6700847. DOI: 10.1177/2040622318806848. View

Ahiawodzi P, Djousse L, Ix J, Kizer J, Tracy R, Arnold A . Non-Esterified Fatty Acids and Risks of Frailty, Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study. J Am Geriatr Soc. 2020; 68(12):2890-2897. PMC: 8285064. DOI: 10.1111/jgs.16793. View

Jadoon Khan M, Alam M, Waldeck-Weiermair M, Karsten F, Groschner L, Riederer M . Inhibition of autophagy rescues palmitic acid-induced necroptosis of endothelial cells. J Biol Chem. 2012; 287(25):21110-20. PMC: 3375534. DOI: 10.1074/jbc.M111.319129. View

Lee S, Park J, Kim H, Kim H, Lee S, Chung W . Palmitate induces lipoapoptosis in Schwann cells through ROS generation-mediated STAMP2 downregulation. Biochem Biophys Res Commun. 2018; 503(3):1260-1266. DOI: 10.1016/j.bbrc.2018.07.034. View

10.

Gill T, Kurland B . The burden and patterns of disability in activities of daily living among community-living older persons. J Gerontol A Biol Sci Med Sci. 2003; 58(1):70-5. DOI: 10.1093/gerona/58.1.m70. View

11.

Morrison W, Smith L . PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. J Lipid Res. 1964; 5:600-8. View

12.

Zock P, de Vries J, Katan M . Impact of myristic acid versus palmitic acid on serum lipid and lipoprotein levels in healthy women and men. Arterioscler Thromb. 1994; 14(4):567-75. DOI: 10.1161/01.atv.14.4.567. View

13.

Kuo H, Bean J, Yen C, Leveille S . Linking C-reactive protein to late-life disability in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. J Gerontol A Biol Sci Med Sci. 2006; 61(4):380-7. PMC: 2376837. DOI: 10.1093/gerona/61.4.380. View

14.

Benjamini Y, Yekutieli D . Quantitative trait Loci analysis using the false discovery rate. Genetics. 2005; 171(2):783-90. PMC: 1456787. DOI: 10.1534/genetics.104.036699. View

15.

Navarini L, Afeltra A, Gallo Afflitto G, Margiotta D . Polyunsaturated fatty acids: any role in rheumatoid arthritis?. Lipids Health Dis. 2017; 16(1):197. PMC: 5634864. DOI: 10.1186/s12944-017-0586-3. View

16.

Fielding B, Callow J, OWEN R, Samra J, Matthews D, Frayn K . Postprandial lipemia: the origin of an early peak studied by specific dietary fatty acid intake during sequential meals. Am J Clin Nutr. 1996; 63(1):36-41. DOI: 10.1093/ajcn/63.1.36. View

17.

Boden G, Chen X, Ruiz J, White J, Rossetti L . Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest. 1994; 93(6):2438-46. PMC: 294452. DOI: 10.1172/JCI117252. View

18.

Psaty B, Delaney J, Arnold A, Curtis L, Fitzpatrick A, Heckbert S . Study of Cardiovascular Health Outcomes in the Era of Claims Data: The Cardiovascular Health Study. Circulation. 2015; 133(2):156-64. PMC: 4814341. DOI: 10.1161/CIRCULATIONAHA.115.018610. View

19.

EATON R, Berman M, Steinberg D . Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. J Clin Invest. 1969; 48(8):1560-79. PMC: 322383. DOI: 10.1172/JCI106122. View

20.

Heimberg M, DUNN G, Wilcox G . The derivation of plasma-free fatty acids from dietary neutral fat in man. J Lab Clin Med. 1974; 83(3):393-402. View