FAHFA footprint in the visceral fat of mice across their lifespan

Zhu, Quan-Fei; Yan, Jingwen; Ni, Jian; Feng, Yun

doi:10.1016/j.bbalip.2020.158639

Cited by 21 publications

(28 citation statements)

References 29 publications

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“…Recently, an increasing number of FAHFA families and hundreds of regioisomers have been identified in humans, animals, and plants ( 7 , 8 , 9 , 11 ). However, the biological functions of only a few FAHFA family members have been reported ( 7 , 13 , 14 , 16 , 20 , 21 , 22 , 23 , 27 , 37 , 38 , 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

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Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

Aryal

Syed

Lee

et al. 2021

Journal of Lipid Research

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Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids with antidiabetic and anti-inflammatory effects. Each FAHFA family consists of esters with different acyl chains and multiple isomers with branch points at different carbons. Some FAHFAs, including palmitic acid hydroxy stearic acids (PAHSAs), improve insulin sensitivity and glucose tolerance in mice by enhancing glucose-stimulated insulin secretion (GSIS), insulin-stimulated glucose transport, and insulin action to suppress hepatic glucose production and reducing adipose tissue inflammation. However, little is known about the biological effects of other FAHFAs. Here, we investigated whether PAHSAs, oleic acid hydroxy stearic acid, palmitoleic acid hydroxy stearic acid, and stearic acid hydroxy stearic acid potentiate GSIS in β-cells and human islets, insulin-stimulated glucose uptake in adipocytes, and anti-inflammatory effects in immune cells. We also investigated whether they activate G protein–coupled receptor 40, which mediates the effects of PAHSAs on insulin secretion and sensitivity in vivo. We show that many FAHFAs potentiate GSIS, activate G protein–coupled receptor 40, and attenuate LPS-induced chemokine and cytokine expression and secretion and phagocytosis in immune cells. However, fewer FAHFAs augment insulin-stimulated glucose uptake in adipocytes. S-9-PAHSA, but not R-9-PAHSA, potentiated GSIS and glucose uptake, while both stereoisomers had anti-inflammatory effects. FAHFAs containing unsaturated acyl chains with higher branching from the carboxylate head group are more likely to potentiate GSIS, whereas FAHFAs with lower branching are more likely to be anti-inflammatory. This study provides insight into the specificity of the biological actions of different FAHFAs and could lead to the development of FAHFAs to treat metabolic and immune-mediated diseases.

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Section: Discussionmentioning

confidence: 99%

“…Recently, Zhu et al. ( 8 ) identified 51 different FAHFA families, including 301 regioisomers in mouse visceral adipose tissue. The number of FAHFA families and regioisomers in mice increased with age ( 8 ).…”

mentioning

confidence: 99%

Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

Aryal

Syed

Lee

et al. 2021

Journal of Lipid Research

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“…Another type of adipose-derived lipokine is fatty acid esters of hydroxy fatty acids (FAHFAs), which are composed of one fatty acid molecule and one hydroxy fatty acid molecule on an ester bond [61]. A total of 51 families of FAHFA exist in both WAT and BAT [62].…”

Section: Adipokines Lipokines and Endocrine Disruption In Obesitymentioning

confidence: 99%

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

2020

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In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.

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“…This observation is surprising; however, it needs further investigation whether nutrition or the endogenous metabolism is responsible for the finding. Interestingly, a recent study in mice could show significant correlations between age and FAHFA levels at least in visceral adipose tissue ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Are Associated With Diet, BMI, and Age

et al. 2021

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Background: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a group of fatty acids with potential anti-inflammatory and anti-diabetic effects. The blood levels of FAHFAs and their regulation in humans have hardly been studied.Objective: We aimed to investigate serum FAHFA levels in well-characterized human cohorts, to evaluate associations with age, sex, BMI, weight loss, diabetic status, and diet.Methods: We analyzed levels of stearic-acid-9-hydroxy-stearic-acid (9-SAHSA), oleic-acid-9-hydroxy-stearic-acid (9-OAHSA) and palmitic-acid-9-hydroxy-palmitic-acid (9-PAHPA) as well as different palmitic acid-hydroxy-stearic-acids (PAHSAs) by HPLC-MS/MS with the use of an internal standard in various cohorts: A cohort of different age groups (18–25y; 40–65y; 75–85y; Σn = 60); severely obese patients undergoing bariatric surgery and non-obese controls (Σn = 36); obese patients with and without diabetes (Σn = 20); vegetarians/vegans (n = 10) and omnivores (n = 9); and young men before and after acute overfeeding with saturated fatty acids (SFA) (n = 15).Results: Omnivores had substantially higher FAHFA levels than vegetarians/vegans [median (25th percentile; 75th percentile) tFAHFAs = 12.82 (7.57; 14.86) vs. 5.86 (5.10; 6.71) nmol/L; P < 0.05]. Dietary overfeeding by supplementation of SFAs caused a significant increase within 1 week [median tFAHFAs = 4.31 (3.31; 5.27) vs. 6.96 (6.50; 7.76) nmol/L; P < 0.001]. Moreover, obese patients had lower FAHFA levels than non-obese controls [median tFAHFAs = 3.24 (2.80; 4.30) vs. 5.22 (4.18; 7.46) nmol/L; P < 0.01] and surgery-induced weight loss increased 9-OAHSA level while other FAHFAs were not affected. Furthermore, significant differences in some FAHFA levels were found between adolescents and adults or elderly, while no differences between sexes and between diabetic and non-diabetic individuals were detected.Conclusions: FAHFA serum levels are strongly affected by high SFA intake and reduced in severe obesity. Age also may influence FAHFA levels, whereas there was no detectable relation with sex and diabetic status. The physiological role of FAHFAs in humans remains to be better elucidated.Trial Registration: All studies referring to these analyses were registered in the German Clinical Trial Register (https://www.drks.de/drks_web/) with the numbers DRKS00009008, DRKS00010133, DRKS00006211, and DRKS00009797.

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FAHFA footprint in the visceral fat of mice across their lifespan

Cited by 21 publications

References 29 publications

Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

Distinct biological activities of isomers from several families of branched fatty acid esters of hydroxy fatty acids (FAHFAs)

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Are Associated With Diet, BMI, and Age

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