Associations between serum concentrations of perfluoroalkyl acids and serum lipid levels in a Chinese population

Fu, Yaning; Wang, Tieyu; Fu, Quanliang; Wang, Pei; Lü, Yonglong

doi:10.1016/j.ecoenv.2014.04.039

Cited by 54 publications

(61 citation statements)

References 53 publications

(70 reference statements)

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“…To summarize, we have shown that C57BL/6 and male BALB/c mice exposed to PFOA have significantly increased plasma cholesterol levels when fed Westernized diets, consistent with human observational findings at the national [39] , [14] and community levels [16] , [19] , [60] and in adolescent [18] , [20] and occupational [44] , [56] , [57] , [9] cohorts. As the majority of these human studies are cross-sectional and unable to assess causality, it has been difficult to study causality because of the directionality difference between epidemiologic human and experimental rodent studies [46] .…”

Section: Discussionsupporting

confidence: 83%

“…In our mice, the increase in plasma cholesterol occurred in the HDL fraction. In humans, significant increases in LDL with increasing PFOA have been seen in national adolescent studies [20] , [75] , exposed communities [60] , [16] , [18] , [19] and occupational cohorts [56] . Human HDL cholesterol and PFOA studies are less consistent, though all show a decrease in HDL as PFOA increases [20] , [21] , [47] , [66] .…”

Section: Discussionmentioning

confidence: 99%

“…In a study of population co-exposed to PFOA and perfluorooctanoate sulfonate, expression of genes involved in reverse cholesterol transport expression, a cause of hypercholesterolemia, were reduced with PFOA exposure [17] . In addition, PFOA exposure has been significantly associated with an increased risk of clinical hypercholesterolemia [60] , [18] and increased plasma cholesterol concentrations in national population studies [39] , [14] , [20] , [75] , in communities near perfluoroalkyl production facilities [60] , [18] , [16] , [19] and in perfluoroalkyl workers [9] , [26] , [56] , [57] . While most studies have been cross-sectional, significant associations between PFOA and cholesterol have been found in exposed communities [16] , [71] and occupational cohorts as well [9] , [56] , [57] though increases attributable to PFOA are small compared to other hypercholesteremic factors [44] .…”

Section: Introductionmentioning

confidence: 99%

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Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

et al. 2016

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Perfluorooctanoic acid (PFOA) is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

et al. 2016

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“…In humans, CYP7A1 deficiency promotes hypercholesterolemia (Beigneux et al, 2002, Pullinger et al, 2002). Epidemiological evidence of individuals exposed to PFOA or PFOS suggest a positive correlation between exposure and increased serum cholesterol (Fu et al, 2014, Geiger et al, 2014, Kerger et al, 2011). Thus, the observed increase in cholesterol in humans exposed to PFOA or PFOS potentially results from a loss of HNF4α function and decreased CYP7A1 transcription.…”

Section: Discussionmentioning

confidence: 99%

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Beggs

McGreal

McCarthy

et al. 2016

Toxicology and Applied Pharmacology

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Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers.

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“…Fu et al. () performed a small (N = 133) cross‐sectional study of the association between PFOS and PFOA and blood lipids in a Chinese sample aged 0–80 (mean 30) years, coming for a health check‐up. Analyses were adjusted for age, gender and BMI, but there was no information on use of lipid‐lowering medications.…”

Section: Assessmentmentioning

confidence: 99%

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

180

199

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half-lives for PFOS and PFOA are about 5 years and 2-4 years, respectively. The derivation of a health-based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.

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Associations between serum concentrations of perfluoroalkyl acids and serum lipid levels in a Chinese population

Cited by 54 publications

References 53 publications

Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

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