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

Kellerer, Teresa; Kleigrewe, Karin; Brandl, Beate; Hofmann, Thomas; Hauner, Hans; Skurk, Thomas

doi:10.3389/fnut.2021.691401

Cited by 28 publications

(32 citation statements)

References 39 publications

(86 reference statements)

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“…The recently recognized beneficial anti-inflammatory and antidiabetic properties of FAHFAs unlock multiple potential applications within the pharmaceutical and health sectors . Synthetic chemistry displays promising potential in producing novel phospholipid species with projected enhanced health characteristics through the incorporation of FAHFAs into significantly less biodegradable glycerophosphates.…”

Section: Resultsmentioning

confidence: 99%

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs

Bogojevic,

Zhang,

Wolff

et al. 2023

J. Org. Chem.

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Fatty acid esters of hydroxy fatty acids (FAHFAs), a newly discovered class of human endogenous complex lipids showing great promise for treating diabetes and inflammatory diseases, exist naturally in extremely low concentrations. This work reports a chemo-enzymatic approach for the comprehensive synthesis of phospholipids containing FAHFAs via sequential steps: hydratase-catalyzed hydration of unsaturated fatty acids to generate structurally diverse hydroxy fatty acids (HFAs), followed by the selective esterification of these HFAs with fatty acids mediated by secondary alcohol-specific Candida antarctica lipase A (CALA), resulting in the formation of a series of diverse FAHFA analogs. The final synthesis is completed through carbodiimidebased coupling of FAHFAs with glycerophosphatidylcholine. Optimal reaction conditions are identified for each step, and the substrate affinity of CALA, responsible for the catalytic mechanisms during FAHFA production, is evaluated through molecular docking. Compared to multistep lab-tedious chemical synthesis, this route, relying on natural building blocks and natural biocatalysts, is significantly facile, scalable, and highly selective, affording high yields (74−98 mol %) in each step for the construction of higher FAHFA-PC series (10/12/13-FAHFAs). The developed strategy aims to increase the availability of naturally occurring FAHFA species and provide the tools for the construction of versatile and novel analogs of FAHFA conjugates.

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Section: Resultsmentioning

confidence: 99%

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs

Bogojevic,

Zhang,

Wolff

et al. 2023

J. Org. Chem.

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“…The levels of PAHSAs are strongly correlated with insulin sensitivity 1,14 and are lower in the adipose tissue and serum of patients with obesity and diabetes than in those without obesity. 3,15 High-fat diet-fed GPR120-deficient mice exhibit severe peripheral blood insulin resistance and significantly reduced insulin sensitivity. 16 In humans and rodents with T2D, GLUT4 is also selectively downregulated in adipose tissue.…”

Section: Pahsas Promote Insulin-stimulated Glucose Uptakementioning

confidence: 99%

“…When necessary, fat is converted to glucose to maintain blood glucose stability. The levels of PAHSAs are strongly correlated with insulin sensitivity 1,14 and are lower in the adipose tissue and serum of patients with obesity and diabetes than in those without obesity 3,15 . High‐fat diet‐fed GPR120‐deficient mice exhibit severe peripheral blood insulin resistance and significantly reduced insulin sensitivity 16 .…”

Section: Fahfas Modulate Diabetesmentioning

confidence: 99%

“…FAHFAs are not only found in conventional foods such as rice and eggs 2,3 but can also be endogenously synthesized by human white adipose tissue (WAT) and the meibomian gland. 4 Nowadays, there is a shortage of drugs available to fundamentally protect or treat diabetes as well as heart and brain disorders.…”

Section: Introductionmentioning

confidence: 99%

“…The FAHFA family consists of a large number of members with distinctive structures according to the different positions of fatty acids (FAs) and hydroxy fatty acids (HFAs). FAHFAs are not only found in conventional foods such as rice and eggs 2,3 but can also be endogenously synthesized by human white adipose tissue (WAT) and the meibomian gland 4 . Nowadays, there is a shortage of drugs available to fundamentally protect or treat diabetes as well as heart and brain disorders.…”

Section: Introductionmentioning

confidence: 99%

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Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity‐related diseases

Li,

Wang,

Jiao

et al. 2024

Obesity Reviews

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SummaryObesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti‐inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure–activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in‐depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed.

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A lipidomic and metabolomic signature of a very low-carbohydrate high-fat diet and high-intensity interval training: an additional analysis of a randomized controlled clinical trial

Cipryan,

Kosek,

García

et al. 2023

Metabolomics

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Introduction Regular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well understood. Metabolomics may have a promising research potential to extend our knowledge and use it in the attempts to find a long-term and sustainable personalized approach in exercise and diet recommendations. Objective The main aim was to investigate the effect of the 12 week very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) on lipidomic and metabolomic profiles in individuals with overweight and obesity. Methods The participants (N = 91) were randomly allocated to HIIT (N = 22), VLCHF (N = 25), VLCHF + HIIT (N = 25) or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4, 8 and 12 weeks. The samples were then subjected to untargeted lipidomic and metabolomic analyses using reversed phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry. Results The VLCHF diet affected plasma lipids considerably while the effect of HIIT was unremarkable. Already after 4 weeks of intervention substantial changes of plasma lipids were found in both VLCHF diet groups. The changes persisted throughout the entire 12 weeks of the VLCHF diet. Specifically, acyl carnitines, plasmalogens, fatty acyl esters of hydroxy fatty acid, sphingomyelin, ceramides, cholesterol esters, fatty acids and 4-hydroxybutyric were identified as lipid families that increased in the VLCHF diet groups whereas lipid families of triglycerides and glycerophospholipids decreased. Additionally, metabolomic analysis showed a decrease of theobromine. Conclusions This study deciphers the specific responses to a VLCHF diet, HIIT and their combination by analysing untargeted lipidomic and metabolomic profile. VLCHF diet caused divergent changes of plasma lipids and other metabolites when compared to the exercise and control group which may contribute to a better understanding of metabolic changes and the appraisal of VLCHF diet benefits and harms. Clinical Trial Registry number NCT03934476, registered 1st May 2019 https://clinicaltrials.gov/ct2/show/NCT03934476?term=NCT03934476&draw=2&rank=1.

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

Cited by 28 publications

References 39 publications

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs

A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs

Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity‐related diseases

A lipidomic and metabolomic signature of a very low-carbohydrate high-fat diet and high-intensity interval training: an additional analysis of a randomized controlled clinical trial

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