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Cited by 152Diabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic DiseasesDiet, Metabolism, and Disease

Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease

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Henderson, Gregory C.·2021·Nutrients
DOI 10.3390/nu13082590PMC PMC8402049
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Abstract

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual’s postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.

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  • Under physiological conditions, FFAs circulate in the blood primarily in an albumin-bound state, but only the unbound fraction is biologically active and amounts to just 1.6 nM, which is less than 10−5 of total FFAs.

    “Under physiological conditions, FFAs circulate in the blood primarily in an albumin-bound state [138,141,142]. However, only the unbound fraction is biologically active and amounts to just 1.6 nM, which is less than 10−5 of total FFAs [141].”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [142]

    The Introduction states that circulating FFAs are predominantly bound to albumin. Neither that passage nor the additional passages retrieved from our copy state that only unbound FFAs are biologically active, or give an unbound concentration of 1.6 nM or a fraction below 10−5 of total FFAs. (LLM, conf=0.87)

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Authors
Henderson, G. C.
Affiliations
Purdue University West Lafayette (US)
Corresponding author
Henderson, Gregory C.
ORCID
Henderson, Gregory C.
Venue
Nutrients
Publisher
MDPI AG
Published
2021-07-28
Volume
13
Issue
8
Pages
2590
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu13082590
PMC
PMC8402049
OpenAlex
W3184787320
Cited by
152
References
142
Citations by year
2026: 19 · 2025: 37 · 2024: 44 · 2023: 39 · 2022: 12 · 2021: 1
FWCI
3.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
McKinley Educational Initiative (N/A)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
plasma free fatty acids, modifiable risk factors, metabolic disorders, insulin resistance, non-alcoholic fatty liver disease, type 2 diabetes, obesity, cardiovascular disease, ectopic fat deposition, adipose tissue lipolysis, caloric restriction, weight loss, physical activity, sleep, cigarette smoking
MeSH terms
Adipose Tissue, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Humans, Insulin Resistance, Life Style, Lipolysis, Metabolic Diseases, Obesity, Risk Factors, Weight Loss, Sleep Apnea, Obstructive, Metabolic Syndrome, Caloric Restriction, Non-alcoholic Fatty Liver Disease

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