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ABSTRACT

Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time.

subcutaneous adipose tissue, US, linoleic acid, dietary linoleic acid, change over time

Introduction

Linoleic acid (LA) (18:2n–6) is an 18-carbon n–6 PUFA with diverse effects on human physiology. LA is linked to skin barrier (1), immune (2), cardiovascular (3, 4), and neurobiological (5) functions, and, as a precursor of arachidonic acid and its metabolites, to reproductive (6), thermoregulatory, and digestive functions (7). In addition, LA is a natural ligand for PPARs (8). PPARs are intimately involved in the regulation of metabolic functions, including lipid and glucose metabolism, and they have been implicated in obesity and cardiometabolic disease risk (9). PPARα agonism may contribute to the ability of dietary LA to reduce circulating concentrations of total and LDL cholesterol (10). Finally, LA can influence biological processes via its nonenzymatic oxidation products. Oxidation of lipids in LDL is a risk marker for coronary heart disease (11). Because of its abundance in LDL and susceptibility to oxidation, LA is the most commonly oxidized species in LDL (12). The LA content of LDL reflects dietary intake (13).

Many seed oils are rich in LA, and consumption in the United States has increased substantially over the last half century (14). Much of this increase has come from soybean oil, which contains between 50% and 60% of total FAs as LA (14). Adipose tissue concentration of LA is particularly responsive to dietary LA, as demonstrated by diet modification trials (10). As such, it is used as a biomarker of dietary intake (15). We hypothesized that increases in dietary LA in the US food system have led to increased adipose tissue concentrations of LA. To test this hypothesis, we conducted a systematic literature review of studies that have reported the LA concentration of subcutaneous adipose tissue. Our findings suggest that adipose tissue LA has more than doubled in the United States over the last half century and correlates strongly with LA in the US food supply, potentially influencing numerous aspects of human physiology and pathophysiology.

Methods

To identify studies, a systematic search was conducted in May 2015 with the use of the PubMed and Google Scholar databases. Search terms included “adipose tissue fatty acids,” “adipose tissue” and “fatty acids,” and “adipose linoleic acid” and “adipose 18:2.” Manuscripts were manually searched for additional references. All studies that reported adipose tissue LA concentration in US subjects before May 2015 were considered. Studies were excluded if subjects were infants, followed an atypical diet, or were diagnosed with a disease or had morbid obesity that could substantially influence FA concentrations in adipose tissue. We excluded nonsubcutaneous adipose depots because of potential differences in FA composition. In cases in which data from a study were reported in more than one publication, only results from the first report were included.

When provided in the manuscript, the date of adipose tissue sampling was used for analyses. When the date of sampling was not provided, the date of publication was used. Nineteen publications provided a sampling date, whereas 18 did not. More recent publications were more likely to provide a sampling date. In cases in which the date provided was a range, the mean value was used.

US LA intake data between 1909 and 1999 were estimated from USDA Economic Research Service food disappearance data, as previously described (14). A tabular version of the data was generously provided by Joseph R Hibbeln, MD (National Institute of Alcohol Abuse and Alcoholism). These data do not extend beyond 1999, and therefore the correlation analysis between LA intake and adipose tissue LA also does not extend beyond that date.

Statistics were performed in publicly available R software. Statistical significance was determined with the use of linear regression analysis.

Results

We identified 37 studies that met inclusion criteria, reporting 38 measurements of subcutaneous adipose tissue LA (Table 1). Publication dates ranged from 1959 to 2008, with no studies identified after this period. The most common sampling site was the buttocks (n = 20), although data also represent abdominal (n = 7), breast adipose (n = 4), posterior iliac crest (n = 2), calf (n = 1), perineum (n = 1), and unspecified subcutaneous adipose tissue (n = 3).

TABLE 1

Studies included in the analysis1

PublicationDate% LASample dateSiteNotes
Hirsch et al. (16) 1960 9.9 NS Buttocks  
Gellhorn et al. (17) 1961 9.5 NS Unspecified SC  
Scott et al. (18) 1962 9.5 NS Abdominal SC  
Hegsted et al. (19) 1962 7.9 NS Unspecified SC  
Dayton et al. (20) 1962 9 1959 Buttocks Baseline 
Lee et al. (21) 1962 12.1, 11.2 NS Buttocks US whites and blacks 
Lee et al. (22) 1962 11.55 NS Buttocks Nondiabetics 
Sweeney et al. (23) 1963 10.6 NS Perineum SC Mothers 
Remenchik et al. (24) 1963 7.56 NS Abdominal SC  
Christakis et al. (25) 1965 9.7 NS Buttocks Baseline 
Rabinowitz et al. (26) 1965 8.7 NS Abdominal SC Baseline 
Dayton et al. (10) 1966 11 1961 (estimated) Buttocks  
Insull et al. (27) 1967 9.2 1962 Abdominal SC  
Fleischman et al. (28) 1968 11 NS Buttocks Baseline 
Baker et al. (29) 1969 8.2 NS Abdominal SC Adults 
Insull et al. (30) 1969 10.21 1966 Abdominal SC  
Insull et al. (31) 1970 10.2 1962, 1966 Abdominal SC US whites and blacks 
Witting et al. (32) 1975 13 1973 Buttocks  
Kokatnur et al. (33) 1979 11.5 1969–1971 Buttocks  
Fordyce et al. (34) 1983 13.68 NS Posterior iliac crest US-born Americans 
Berry et al. (35) 1986 16.3 1981–1982 Buttocks  
Hill et al. (36) 1987 15.8 NS Breast adipose Controls 
Handelman et al. (37) 1988 18.2 1986 Buttocks  
Malcom et al. (38) 1989 15.37 1986–1987 Buttocks  
Hudgins et al. (39) 1991 16.91 1981 Buttocks  
London et al. (40) 1991 17.23 1986–1987 Buttocks  
Hunter et al. (41) 1992 19 1986–1987 Buttocks  
London et al. (42) 1993 17.72 1986–1988 Buttocks  
Phinney et al. (43) 1994 18.72 NS Unspecified SC  
Godley et al. (44) 1996 17.57 1989–1991 Buttocks  
Petrek et al. (45) 1997 16.59 1987–1989 Breast adipose  
Garland et al. (46) 1998 18.5 1986–1987 Buttocks  
Ullrich et al. (47) 2001 18 NS Posterior iliac crest Controls 
Bagga et al. (48) 2002 13.9 1995–1996 Breast adipose Controls 
Knutsen et al. (49) 2003 20.1 NS Buttocks  
Ren et al. (50) 2008 23.4 NS Calf SC  
Yee et al. (51) 2010 18 2006–2008 Breast adipose Baseline 
PublicationDate% LASample dateSiteNotes
Hirsch et al. (16) 1960 9.9 NS Buttocks  
Gellhorn et al. (17) 1961 9.5 NS Unspecified SC  
Scott et al. (18) 1962 9.5 NS Abdominal SC  
Hegsted et al. (19) 1962 7.9 NS Unspecified SC  
Dayton et al. (20) 1962 9 1959 Buttocks Baseline 
Lee et al. (21) 1962 12.1, 11.2 NS Buttocks US whites and blacks 
Lee et al. (22) 1962 11.55 NS Buttocks Nondiabetics 
Sweeney et al. (23) 1963 10.6 NS Perineum SC Mothers 
Remenchik et al. (24) 1963 7.56 NS Abdominal SC  
Christakis et al. (25) 1965 9.7 NS Buttocks Baseline 
Rabinowitz et al. (26) 1965 8.7 NS Abdominal SC Baseline 
Dayton et al. (10) 1966 11 1961 (estimated) Buttocks  
Insull et al. (27) 1967 9.2 1962 Abdominal SC  
Fleischman et al. (28) 1968 11 NS Buttocks Baseline 
Baker et al. (29) 1969 8.2 NS Abdominal SC Adults 
Insull et al. (30) 1969 10.21 1966 Abdominal SC  
Insull et al. (31) 1970 10.2 1962, 1966 Abdominal SC US whites and blacks 
Witting et al. (32) 1975 13 1973 Buttocks  
Kokatnur et al. (33) 1979 11.5 1969–1971 Buttocks  
Fordyce et al. (34) 1983 13.68 NS Posterior iliac crest US-born Americans 
Berry et al. (35) 1986 16.3 1981–1982 Buttocks  
Hill et al. (36) 1987 15.8 NS Breast adipose Controls 
Handelman et al. (37) 1988 18.2 1986 Buttocks  
Malcom et al. (38) 1989 15.37 1986–1987 Buttocks  
Hudgins et al. (39) 1991 16.91 1981 Buttocks  
London et al. (40) 1991 17.23 1986–1987 Buttocks  
Hunter et al. (41) 1992 19 1986–1987 Buttocks  
London et al. (42) 1993 17.72 1986–1988 Buttocks  
Phinney et al. (43) 1994 18.72 NS Unspecified SC  
Godley et al. (44) 1996 17.57 1989–1991 Buttocks  
Petrek et al. (45) 1997 16.59 1987–1989 Breast adipose  
Garland et al. (46) 1998 18.5 1986–1987 Buttocks  
Ullrich et al. (47) 2001 18 NS Posterior iliac crest Controls 
Bagga et al. (48) 2002 13.9 1995–1996 Breast adipose Controls 
Knutsen et al. (49) 2003 20.1 NS Buttocks  
Ren et al. (50) 2008 23.4 NS Calf SC  
Yee et al. (51) 2010 18 2006–2008 Breast adipose Baseline 
1

LA, linoleic acid; NS, not specified; SC, subcutaneous adipose tissue.

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TABLE 1

Studies included in the analysis1

PublicationDate% LASample dateSiteNotes
Hirsch et al. (16) 1960 9.9 NS Buttocks  
Gellhorn et al. (17) 1961 9.5 NS Unspecified SC  
Scott et al. (18) 1962 9.5 NS Abdominal SC  
Hegsted et al. (19) 1962 7.9 NS Unspecified SC  
Dayton et al. (20) 1962 9 1959 Buttocks Baseline 
Lee et al. (21) 1962 12.1, 11.2 NS Buttocks US whites and blacks 
Lee et al. (22) 1962 11.55 NS Buttocks Nondiabetics 
Sweeney et al. (23) 1963 10.6 NS Perineum SC Mothers 
Remenchik et al. (24) 1963 7.56 NS Abdominal SC  
Christakis et al. (25) 1965 9.7 NS Buttocks Baseline 
Rabinowitz et al. (26) 1965 8.7 NS Abdominal SC Baseline 
Dayton et al. (10) 1966 11 1961 (estimated) Buttocks  
Insull et al. (27) 1967 9.2 1962 Abdominal SC  
Fleischman et al. (28) 1968 11 NS Buttocks Baseline 
Baker et al. (29) 1969 8.2 NS Abdominal SC Adults 
Insull et al. (30) 1969 10.21 1966 Abdominal SC  
Insull et al. (31) 1970 10.2 1962, 1966 Abdominal SC US whites and blacks 
Witting et al. (32) 1975 13 1973 Buttocks  
Kokatnur et al. (33) 1979 11.5 1969–1971 Buttocks  
Fordyce et al. (34) 1983 13.68 NS Posterior iliac crest US-born Americans 
Berry et al. (35) 1986 16.3 1981–1982 Buttocks  
Hill et al. (36) 1987 15.8 NS Breast adipose Controls 
Handelman et al. (37) 1988 18.2 1986 Buttocks  
Malcom et al. (38) 1989 15.37 1986–1987 Buttocks  
Hudgins et al. (39) 1991 16.91 1981 Buttocks  
London et al. (40) 1991 17.23 1986–1987 Buttocks  
Hunter et al. (41) 1992 19 1986–1987 Buttocks  
London et al. (42) 1993 17.72 1986–1988 Buttocks  
Phinney et al. (43) 1994 18.72 NS Unspecified SC  
Godley et al. (44) 1996 17.57 1989–1991 Buttocks  
Petrek et al. (45) 1997 16.59 1987–1989 Breast adipose  
Garland et al. (46) 1998 18.5 1986–1987 Buttocks  
Ullrich et al. (47) 2001 18 NS Posterior iliac crest Controls 
Bagga et al. (48) 2002 13.9 1995–1996 Breast adipose Controls 
Knutsen et al. (49) 2003 20.1 NS Buttocks  
Ren et al. (50) 2008 23.4 NS Calf SC  
Yee et al. (51) 2010 18 2006–2008 Breast adipose Baseline 
PublicationDate% LASample dateSiteNotes
Hirsch et al. (16) 1960 9.9 NS Buttocks  
Gellhorn et al. (17) 1961 9.5 NS Unspecified SC  
Scott et al. (18) 1962 9.5 NS Abdominal SC  
Hegsted et al. (19) 1962 7.9 NS Unspecified SC  
Dayton et al. (20) 1962 9 1959 Buttocks Baseline 
Lee et al. (21) 1962 12.1, 11.2 NS Buttocks US whites and blacks 
Lee et al. (22) 1962 11.55 NS Buttocks Nondiabetics 
Sweeney et al. (23) 1963 10.6 NS Perineum SC Mothers 
Remenchik et al. (24) 1963 7.56 NS Abdominal SC  
Christakis et al. (25) 1965 9.7 NS Buttocks Baseline 
Rabinowitz et al. (26) 1965 8.7 NS Abdominal SC Baseline 
Dayton et al. (10) 1966 11 1961 (estimated) Buttocks  
Insull et al. (27) 1967 9.2 1962 Abdominal SC  
Fleischman et al. (28) 1968 11 NS Buttocks Baseline 
Baker et al. (29) 1969 8.2 NS Abdominal SC Adults 
Insull et al. (30) 1969 10.21 1966 Abdominal SC  
Insull et al. (31) 1970 10.2 1962, 1966 Abdominal SC US whites and blacks 
Witting et al. (32) 1975 13 1973 Buttocks  
Kokatnur et al. (33) 1979 11.5 1969–1971 Buttocks  
Fordyce et al. (34) 1983 13.68 NS Posterior iliac crest US-born Americans 
Berry et al. (35) 1986 16.3 1981–1982 Buttocks  
Hill et al. (36) 1987 15.8 NS Breast adipose Controls 
Handelman et al. (37) 1988 18.2 1986 Buttocks  
Malcom et al. (38) 1989 15.37 1986–1987 Buttocks  
Hudgins et al. (39) 1991 16.91 1981 Buttocks  
London et al. (40) 1991 17.23 1986–1987 Buttocks  
Hunter et al. (41) 1992 19 1986–1987 Buttocks  
London et al. (42) 1993 17.72 1986–1988 Buttocks  
Phinney et al. (43) 1994 18.72 NS Unspecified SC  
Godley et al. (44) 1996 17.57 1989–1991 Buttocks  
Petrek et al. (45) 1997 16.59 1987–1989 Breast adipose  
Garland et al. (46) 1998 18.5 1986–1987 Buttocks  
Ullrich et al. (47) 2001 18 NS Posterior iliac crest Controls 
Bagga et al. (48) 2002 13.9 1995–1996 Breast adipose Controls 
Knutsen et al. (49) 2003 20.1 NS Buttocks  
Ren et al. (50) 2008 23.4 NS Calf SC  
Yee et al. (51) 2010 18 2006–2008 Breast adipose Baseline 
1

LA, linoleic acid; NS, not specified; SC, subcutaneous adipose tissue.

Open in new tab

When considering all subcutaneous adipose sites, LA concentration increased in a linear manner over time (R2 = 0.83; P < 0.001) (Figure 1A). The best-fit line for adipose tissue LA increased from 9.1% in 1959 to 21.5% in 2008, representing a 136% increase.

FIGURE 1
US adipose tissue LA concentration, 1959–2008. Increase in adipose tissue LA concentration over time across all subcutaneous sites (R2 = 0.83; P < 0.001) (A). Increase in adipose tissue LA concentration over time, buttocks and abdominal subcutaneous only (R2 = 0.86; P < 0.001) (B). LA, linoleic acid.
Open in new tabDownload slide

US adipose tissue LA concentration, 1959–2008. Increase in adipose tissue LA concentration over time across all subcutaneous sites (R2 = 0.83; P < 0.001) (A). Increase in adipose tissue LA concentration over time, buttocks and abdominal subcutaneous only (R2 = 0.86; P < 0.001) (B). LA, linoleic acid.

FIGURE 1
US adipose tissue LA concentration, 1959–2008. Increase in adipose tissue LA concentration over time across all subcutaneous sites (R2 = 0.83; P < 0.001) (A). Increase in adipose tissue LA concentration over time, buttocks and abdominal subcutaneous only (R2 = 0.86; P < 0.001) (B). LA, linoleic acid.
Open in new tabDownload slide

US adipose tissue LA concentration, 1959–2008. Increase in adipose tissue LA concentration over time across all subcutaneous sites (R2 = 0.83; P < 0.001) (A). Increase in adipose tissue LA concentration over time, buttocks and abdominal subcutaneous only (R2 = 0.86; P < 0.001) (B). LA, linoleic acid.

To eliminate possible confounding because of differences in adipose tissue composition across subcutaneous sites, we repeated the analysis including only data from the buttocks and abdominal tissue, which have a comparable FA composition (38). This had little impact on the strength of the relation between time and adipose tissue LA (R2 = 0.86; P < 0.001) (Figure 1B).

Dietary LA has been shown to influence adipose tissue LA concentration in diet modification trials; however, to our knowledge, this hypothesis has never been evaluated by interrogating the correlation between LA intake and adipose tissue LA in a free-living population over a long period of time. Considering all subcutaneous sites, dietary intake of LA was highly correlated with adipose tissue LA (R2 = 0.81; P < 0.001) (Figure 2). For every kg increase of yearly per capita LA intake, adipose tissue concentration of LA increased by 2%.

FIGURE 2
Correlation between adipose tissue LA concentration (all sites) and dietary LA intake, 1959–1999. Adipose tissue LA concentration is strongly correlated with dietary LA intake (R2 = 0.81; P < 0.001). LA, linoleic acid.
Open in new tabDownload slide

Correlation between adipose tissue LA concentration (all sites) and dietary LA intake, 1959–1999. Adipose tissue LA concentration is strongly correlated with dietary LA intake (R2 = 0.81; P < 0.001). LA, linoleic acid.

FIGURE 2
Correlation between adipose tissue LA concentration (all sites) and dietary LA intake, 1959–1999. Adipose tissue LA concentration is strongly correlated with dietary LA intake (R2 = 0.81; P < 0.001). LA, linoleic acid.
Open in new tabDownload slide

Correlation between adipose tissue LA concentration (all sites) and dietary LA intake, 1959–1999. Adipose tissue LA concentration is strongly correlated with dietary LA intake (R2 = 0.81; P < 0.001). LA, linoleic acid.

Conclusions

These findings support the hypothesis that adipose tissue LA concentration has greatly increased in the United States over the last half century. Between 1959 and 2008, adipose tissue LA increased by 136%, representing a major shift in the adipose tissue concentration of a bioactive FA.

Because of its influence on multiple physiologic and pathophysiologic processes, LA has the potential to play an important role in human health. At the same time that the LA content of adipose tissue has been increasing, the United States has experienced substantial changes in disease prevalence. Cardiovascular disease risk has declined (52), whereas the prevalence of obesity (53), diabetes (54), and asthma (55) have increased. Our aim was not to evaluate the potential causal role of LA in these pathophysiologic processes, but simply to highlight that a role for LA in these trends is mechanistically possible and worthy of further investigation.

Our findings suggest that adipose tissue LA concentration is strongly correlated with dietary LA intake. This provides additional independent support for the hypothesis that long-term adipose tissue LA concentration is tied to dietary LA intake, and for the first time demonstrates that this relation applies to long-term population trends. Our analysis may also provide a basis for modeling the relation between population LA intake and adipose tissue LA. For each kg increase of estimated yearly per capita LA intake, adipose tissue LA increased by 2%. Because the half-life of LA incorporation into adipose tissue is ∼680 d (10), changes in LA intake would take several years to result in a stable increase of adipose tissue LA.

Limitations of this study relate primarily to the nature of the underlying data. The data were not the result of longitudinal random sampling of the US population, but rather were primarily small samples representing varied regions of the United States. The underlying assumption is that local data, to some extent, represent broader population trends. However, local differences in dietary habits could reduce the applicability of individual data points to the United States as a whole. Furthermore, the results shown here are from laboratories that used different methods (e.g., packed compared with liquid-phase capillary columns or total adipose FAs compared with adipose tissue TG FAs) and reporting (e.g., weight percentage or area percentage). Some of the earlier studies may not have accounted for the longer chain (20- and 22-carbon) PUFAs, effectively increasing the proportion of LA in studies reported in the earlier years. Despite differences in methods that exist in the studies included in this cross-sectional study, we are unaware of any that would produce a large and systematic increase of LA. Our results are also limited by the fact that there are gaps in years of reported studies. In addition, 18 of 37 studies did not provide a sampling date, and therefore we used the publication date in analyses. In these cases, the sampling date occurred before the publication date, but the time difference is unknown. These limitations would all be expected to increase the variability of the data and decrease the likelihood of identifying statistically significant correlations. The fact that we were nevertheless able to identify strong positive relations between adipose tissue LA concentration and time (R2 = 0.81–0.90; P < 0.001) argues that the data were of sufficient quality to address the hypotheses in question. Finally, estimates of LA intake used in Figure 2 are based on food disappearance data (14), which are not a direct measure of food intake. However, food disappearance estimates are likely more accurate than self-reported estimates, such as those from the CDC NHANES surveys, which are the primary alternative (56).

Our findings suggest that adipose tissue LA has increased substantially in the United States over the last half century, and, to our knowledge, for the first time demonstrate that this increase is highly correlated with increased dietary LA intake over the same period. Interestingly, 3 recent investigations (2013–2015) of adipose tissue LA in European countries found concentrations of 11% (57), 12.5% (58), and 10.6% (59). These values are similar to earlier reports from the United States. Because LA is in involved in numerous physiologic and pathophysiologic processes, these changes have potentially significant implications for public health. These findings call for further research into the consequences, positive or negative, of such a major shift in the adipose tissue concentration of a single bioactive FA occurring over a relatively short period of time in the United States.

Acknowledgments

We thank Joseph R Hibbeln for generously providing us with tabular data on US dietary LA intake, and Elizabeth Sosik for statistical consultation. Both authors read and approved the final manuscript.

References

1

Ziboh
VA
.
Prostaglandins, leukotrienes, and hydroxy fatty acids in epidermis
.
Semin Dermatol
1992
;
11
:
114
–
20
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
2

Harbige
LS
.
Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease
.
Proc Nutr Soc
1998
;
57
:
555
–
62
.

Google Scholar

Crossref
Search ADS
PubMed

 
3

Farvid
MS
,
Ding
M
,
Pan
A
,
Sun
Q
,
Chiuve
SE
,
Steffen
LM
,
Willett
WC
,
Hu
FB
.
Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies
.
Circulation
2014
;
130
:
1568
–
78
.

Google Scholar

Crossref
Search ADS
PubMed

 
4

Ramsden
CE
,
Zamora
D
,
Leelarthaepin
B
,
Majchrzak-Hong
SF
,
Faurot
KR
,
Suchindran
CM
,
Ringel
A
,
Davis
JM
,
Hibbeln
JR
.
Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis
.
BMJ
2013
;
346
:
e8707
.

Google Scholar

Crossref
Search ADS
PubMed

 
5

Gibson
RA
,
Muhlhausler
B
,
Makrides
M
.
Conversion of linoleic acid and alpha-linolenic acid to long-chain polyunsaturated fatty acids (LCPUFAs), with a focus on pregnancy, lactation and the first 2 years of life
.
Matern Child Nutr
2011
;
7
:
17
–
26
.

Google Scholar

Crossref
Search ADS
PubMed

 
6

Thorburn
GD
.
The placenta, PGE2 and parturition
.
Early Hum Dev
1992
;
29
:
63
–
73
.

Google Scholar

Crossref
Search ADS
PubMed

 
7

Funk
CD
.
Prostaglandins and leukotrienes: Advances in eicosanoid biology
.
Science
2001
;
294
:
1871
–
5
.

Google Scholar

Crossref
Search ADS
PubMed

 
8

Kliewer
SA
,
Sundseth
SS
,
Jones
SA
,
Brown
PJ
,
Wisely
GB
,
Koble
CS
,
Devchand
P
,
Wahli
W
,
Willson
TM
,
Lehhard
JM
, et al. 
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ
.
Proc Natl Acad Sci USA
1997
;
94
:
4318
–
23
.

Google Scholar

Crossref
Search ADS
PubMed

 
9

Desvergne
B
,
Wahli
W
.
Peroxisome proliferator-activated receptors: nuclear control of metabolism
.
Endocr Rev
1999
;
20
:
649
–
88
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
10

Dayton
S
,
Hashimoto
S
,
Dixon
W
,
Pearce
ML
.
Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat
.
J Lipid Res
1966
;
7
:
103
–
11
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
11

Meisinger
C
,
Baumert
J
,
Khuseyinova
N
,
Loewel
H
,
Koenig
W
.
Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population
.
Circulation
2005
;
112
:
651
–
7
.

Google Scholar

Crossref
Search ADS
PubMed

 
12

Jira
W
,
Spiteller
G
,
Carson
W
,
Schramm
A
.
Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients
.
Chem Phys Lipids
1998
;
91
:
1
–
11
.

Google Scholar

Crossref
Search ADS
PubMed

 
13

Kratz
M
,
Cullen
P
,
Kannenberg
F
,
Kassner
A
,
Fobker
M
,
Abuja
PM
,
Assmann
G
,
Wahrburg
U
.
Effects of dietary fatty acids on the composition and oxidizability of low-density lipoprotein
.
Eur J Clin Nutr
2002
;
56
:
72
–
81
.

Google Scholar

Crossref
Search ADS
PubMed

 
14

Blasbalg
TL
,
Hibbeln
JR
,
Ramsden
CE
,
Majchrzak
SF
,
Rawlings
RR
.
Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century123
.
Am J Clin Nutr
2011
;
93
:
950
–
62
.

Google Scholar

Crossref
Search ADS
PubMed

 
15

Hodson
L
,
Skeaff
CM
,
Fielding
BA
.
Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake
.
Prog Lipid Res
2008
;
47
:
348
–
80
.

Google Scholar

Crossref
Search ADS
PubMed

 
16

Hirsch
J
,
Farquhar
JW
,
Ahrens
EH
,
Peterson
ML
,
Stoffel
W
.
Studies of adipose tissue in man. A microtechnic for sampling and analysis
.
Am J Clin Nutr
1960
;
8
:
499
–
511
.

Google Scholar

Crossref
Search ADS
PubMed

 
17

Gellhorn
A
,
Marks
PA
.
The composition and biosynthesis of lipids in human adipose tissues
.
J Clin Invest
1961
;
40
:
925
–
32
.

Google Scholar

Crossref
Search ADS
PubMed

 
18

Scott
RF
,
Daoud
AS
,
Gittelsohn
A
,
Opalka
E
,
Florentin
R
,
Goodale
F
.
Lack of correlation between fatty acid patterns in adipose tissue and amount of coronary arteriosclerosis
.
Am J Clin Nutr
1962
;
10
:
250
–
6
.

Google Scholar

Crossref
Search ADS
PubMed

 
19

Hegsted
DM
,
Jack
CW
,
Stare
FJ
.
The composition of human adipose tissue from several parts of the world
.
Am J Clin Nutr
1962
;
10
:
11
–
8
.

Google Scholar

Crossref
Search ADS
PubMed

 
20

Dayton
S
,
Pearce
ML
,
Hashimoto
S
,
Fakler
LJ
,
Hiscock
E
,
Dixon
WJ
.
A controlled clinical trial of a diet high in unsaturated fat. Preliminary observations
.
N Engl J Med
1962
;
266
:
1017
–
23
.

Google Scholar

Crossref
Search ADS
PubMed

 
21

Lee
K
,
Shaper
A
,
Scott
R
,
Goodale
F
,
Thomas
W
.
Geographic studies pertaining to arteriosclerosis: Comparison of fatty acid patterns of adipose tissue and plasma lipids in East Africans with those of North American white and negro groups
.
Arch Pathol
1962
;
74
:
481
–
8
.

Google Scholar

OpenURL Placeholder Text

 
22

Lee
KT
,
Scott
RF
,
Morrison
ES
,
Thomas
WA
.
Chemi-co-anatomic studies of arteriosclerosis and thrombosis in diabetics. II. Fatty acids of adipose tissue and plasma lipids in several groups of North American diabetics and nondiabetics
.
Exp Mol Pathol
1962
;
1
:
364
–
76
.

Google Scholar

Crossref
Search ADS
PubMed

 
23

Sweeney
MJ
,
Etteldorf
JN
,
Throop
LJ
,
Timma
DL
,
Wrenn
EL
.
Diet and fatty acid distribution in subcutaneous fat and the cholesterol-triglyceride fraction of serum of young infants
.
J Clin Invest
1963
;
42
:
1
–
9
.

Google Scholar

Crossref
Search ADS
PubMed

 
24

Remenchik
AP
,
Bernsohn
J
.
Relationships between the composition of adipose tissue and the total fat content of the body
.
Ann N Y Acad Sci
1963
;
110
:
754
–
9
.

Google Scholar

Crossref
Search ADS
PubMed

 
25

Christakis
GJ
,
Rinzler
SH
,
Archer
M
,
Hashim
SA
,
Vanitallie
TB
.
Effect of serum cholesterol-lowering diet on composition of depot fat in man
.
Am J Clin Nutr
1965
;
16
:
243
–
51
.

Google Scholar

Crossref
Search ADS
PubMed

 
26

Rabinowitz
JL
,
Reimenschneider
RW
,
Myerson
RM
.
The effect of L-triiodothyronine on the fatty acid composition of human adipose tissue
.
Metabolism
1965
;
14
:
612
–
8
.

Google Scholar

Crossref
Search ADS
PubMed

 
27

Insull
W
,
Bartsch
GE
.
Fatty acid composition of human adipose tissue related to age, sex, and race
.
Am J Clin Nutr
1967
;
20
:
13
–
23
.

Google Scholar

Crossref
Search ADS
PubMed

 
28

Fleischman
AI
,
Hayton
T
,
Bierenbaum
ML
,
Watson
P
.
The effect of a polyunsaturated diet upon adipose-tissue fatty acids in young coronary males. A five-year cohort study
.
Lipids
1968
;
3
:
147
–
50
.

Google Scholar

Crossref
Search ADS
PubMed

 
29

Baker
GL
.
Human adipose tissue composition and age
.
Am J Clin Nutr
1969
;
22
:
829
–
35
.

Google Scholar

Crossref
Search ADS
PubMed

 
30

Insull
W
,
Lang
PD
,
Hsi
BP
,
Yoshimura
S
.
Studies of arteriosclerosis in Japanese and American men
.
J Clin Invest
1969
;
48
:
1313
–
27
.

Google Scholar

Crossref
Search ADS
PubMed

 
31

Insull
W
,
Lang
PD
,
Hsi
BP
.
Adipose tissue fatty acid differences in American men between 1962 and 1966
.
Am J Clin Nutr
1970
;
23
:
17
–
26
.

Google Scholar

Crossref
Search ADS
PubMed

 
32

Witting
LA
,
Lee
L
.
Recommended dietary allowance for vitamin E: relation to dietary, erythrocyte and adipose tissue linoleate
.
Am J Clin Nutr
1975
;
28
:
577
–
83
.

Google Scholar

Crossref
Search ADS
PubMed

 
33

Kokatnur
MG
,
Oalmann
MC
,
Johnson
WD
,
Malcom
GT
,
Strong
JP
.
Fatty acid composition of human adipose tissue from two anatomical sites in a biracial community
.
Am J Clin Nutr
1979
;
32
:
2198
–
205
.

Google Scholar

Crossref
Search ADS
PubMed

 
34

Fordyce
MK
,
Christakis
G
,
Kafatos
A
,
Duncan
R
,
Cassady
J
.
Adipose tissue fatty acid composition of adolescents in a U.S.–Greece cross-cultural study of coronary heart disease risk factors
.
J Chronic Dis
1983
;
36
:
481
–
6
.

Google Scholar

Crossref
Search ADS
PubMed

 
35

Berry
EM
,
Hirsch
J
,
Most
J
,
McNamara
DJ
,
Thornton
J
.
The relationship of dietary fat to plasma lipid levels as studied by factor analysis of adipose tissue fatty acid composition in a free-living population of middle-aged American men
.
Am J Clin Nutr
1986
;
44
:
220
–
31
.

Google Scholar

Crossref
Search ADS
PubMed

 
36

Hill
P
,
Wynder
EL
.
Comparison of mammary adipose fatty acid composition in Japanese and American breast cancer patients
.
Eur J Cancer Clin Oncol
1987
;
23
:
407
–
10
.

Google Scholar

Crossref
Search ADS
PubMed

 
37

Handelman
GJ
,
Epstein
WL
,
Machlin
LJ
,
van Kuijk
FJ
,
Dratz
EA
.
Biopsy method for human adipose with vitamin E and lipid measurements
.
Lipids
1988
;
23
:
598
–
604
.

Google Scholar

Crossref
Search ADS
PubMed

 
38

Malcom
GT
,
Bhattacharyya
AK
,
Velez-Duran
M
,
Guzman
MA
,
Oalmann
MC
,
Strong
JP
.
Fatty acid composition of adipose tissue in humans: differences between subcutaneous sites
.
Am J Clin Nutr
1989
;
50
:
288
–
91
.

Google Scholar

Crossref
Search ADS
PubMed

 
39

Hudgins
LC
,
Hirsch
J
,
Emken
EA
.
Correlation of isomeric fatty acids in human adipose tissue with clinical risk factors for cardiovascular disease
.
Am J Clin Nutr
1991
;
53
:
474
–
82
.

Google Scholar

Crossref
Search ADS
PubMed

 
40

London
SJ
,
Sacks
FM
,
Caesar
J
,
Stampfer
MJ
,
Siguel
E
,
Willett
WC
.
Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women
.
Am J Clin Nutr
1991
;
54
:
340
–
5
.

Google Scholar

Crossref
Search ADS
PubMed

 
41

Hunter
DJ
,
Rimm
EB
,
Sacks
FM
,
Stampfer
MJ
,
Colditz
GA
,
Litin
LB
,
Willett
WC
.
Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men
.
Am J Epidemiol
1992
;
135
:
418
–
27
.

Google Scholar

Crossref
Search ADS
PubMed

 
42

London
SJ
,
Sacks
FM
,
Stampfer
MJ
,
Henderson
IC
,
Maclure
M
,
Tomita
A
,
Wood
WC
,
Remine
S
,
Robert
NJ
,
Dmochowski
JR
.
Fatty acid composition of the subcutaneous adipose tissue and risk of proliferative benign breast disease and breast cancer
.
J Natl Cancer Inst
1993
;
85
:
785
–
93
.

Google Scholar

Crossref
Search ADS
PubMed

 
43

Phinney
SD
,
Stern
JS
,
Burke
KE
,
Tang
AB
,
Miller
G
,
Holman
RT
.
Human subcutaneous adipose tissue shows site-specific differences in fatty acid composition
.
Am J Clin Nutr
1994
;
60
:
725
–
9
.

Google Scholar

Crossref
Search ADS
PubMed

 
44

Godley
PA
,
Campbell
MK
,
Gallagher
P
,
Martinson
FE
,
Mohler
JL
,
Sandler
RS
.
Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma
.
Cancer Epidemiol Biomark Prev
1996
;
5
:
889
–
95
.

Google Scholar

OpenURL Placeholder Text

 
45

Petrek
JA
,
Hudgins
LC
,
Ho
M
,
Bajorunas
DR
,
Hirsch
J
.
Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis
.
J Clin Oncol
1997
;
15
:
1377
–
84
.

Google Scholar

Crossref
Search ADS
PubMed

 
46

Garland
M
,
Sacks
FM
,
Colditz
GA
,
Rimm
EB
,
Sampson
LA
,
Willett
WC
,
Hunter
DJ
.
The relation between dietary intake and adipose tissue composition of selected fatty acids in US women
.
Am J Clin Nutr
1998
;
67
:
25
–
30
.

Google Scholar

Crossref
Search ADS
PubMed

 
47

Ullrich
NF
,
Purnell
JQ
,
Brunzell
JD
.
Adipose tissue fatty acid composition in humans with lipoprotein lipase deficiency
.
J Investig Med
2001
;
49
:
273
–
5
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
48

Bagga
D
,
Anders
KH
,
Wang
H-J
,
Glaspy
JA
.
Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer
.
Nutr Cancer
2002
;
42
:
180
–
5
.

Google Scholar

Crossref
Search ADS
PubMed

 
49

Knutsen
SF
,
Fraser
GE
,
Beeson
WL
,
Lindsted
KD
,
Shavlik
DJ
.
Comparison of adipose tissue fatty acids with dietary fatty acids as measured by 24-hour recall and food frequency questionnaire in Black and White Adventists: the Adventist Health Study
.
Ann Epidemiol
2003
;
13
:
119
–
27
.

Google Scholar

Crossref
Search ADS
PubMed

 
50

Ren
J
,
Dimitrov
I
,
Sherry
AD
,
Malloy
CR
.
Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla
.
J Lipid Res
2008
;
49
:
2055
–
62
.

Google Scholar

Crossref
Search ADS
PubMed

 
51

Yee
LD
,
Lester
JL
,
Cole
RM
,
Richardson
JR
,
Hsu
JC
,
Li
Y
,
Lehman
A
,
Belury
MA
,
Clinton
SK
.
ω-3 Fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition
.
Am J Clin Nutr
2010
;
91
:
1185
–
94
.

Google Scholar

Crossref
Search ADS
PubMed

 
52

Finegold
JA
,
Asaria
P
,
Francis
DP
.
Mortality from ischaemic heart disease by country, region, and age: Statistics from World Health Organisation and United Nations
.
Int J Cardiol
2013
;
168
:
934
–
45
.

Google Scholar

Crossref
Search ADS
PubMed

 
53

Fryar
CD
,
Carroll
MD
,
Ogden
CL
.
Prevalence of overweight, obesity, and extreme obesity among adults: United States, trends 1960–1962 through 2007
.
Natl Cent Health Stat
2008
;
2012
:
1
–
6
.

Google Scholar

OpenURL Placeholder Text

 
54

Geiss
LS
,
Wang
J
,
Cheng
YJ
,
Thompson
TJ
,
Barker
L
,
Li
Y
,
Albright
AL
,
Gregg
EW
.
Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980–2012
.
JAMA
2014
;
312
:
1218
–
26
.

Google Scholar

Crossref
Search ADS
PubMed

 
55

Allan
K
,
Devereux
G
.
Diet and asthma: nutrition implications from prevention to treatment
.
J Am Diet Assoc
2011
;
111
:
258
–
68
.

Google Scholar

Crossref
Search ADS
PubMed

 
56

Schoeller
DA
,
Thomas
D
,
Archer
E
,
Heymsfield
SB
,
Blair
SN
,
Goran
MI
,
Hill
JO
,
Atkinson
RL
,
Corkey
BE
,
Foreyt
J
, et al. 
Self-report-based estimates of energy intake offer an inadequate basis for scientific conclusions
.
Am J Clin Nutr
2013
;
97
:
1413
–
5
.

Google Scholar

Crossref
Search ADS
PubMed

 
57

Cottet
V
,
Vaysse
C
,
Scherrer
M-L
,
Ortega-Deballon
P
,
Lakkis
Z
,
Delhorme
J-B
,
Deguelte-Lardière
S
,
Combe
N
,
Bonithon-Kopp
C
.
Fatty acid composition of adipose tissue and colorectal cancer: a case-control study
.
Am J Clin Nutr
2015
;
101
:
192
–
201
.

Google Scholar

Crossref
Search ADS
PubMed

 
58

Kunešová
M
,
Hlavatý
P
,
Tvrzická
E
,
Staňková
B
,
Kalousková
P
,
Viguerie
N
,
Larsen
TM
,
van Baak
MA
,
Jebb
SA
,
Martinez
JA
, et al. 
Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance: the DIOGENES study
.
Physiol Res
2012
;
61
:
597
–
607
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
59

Hellmuth
C
,
Demmelmair
H
,
Schmitt
I
,
Peissner
W
,
Blüher
M
,
Koletzko
B
.
Association between Plasma Nonesterified Fatty Acids Species and Adipose Tissue Fatty Acid Composition. PLoS ONE [Internet]
.
2013
;8 [cited 2015 Jul 29]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788793/.

Author notes

1

The authors report no funding for this study.

2

Author disclosures: SJ Guyenet and SE Carlson, no conflicts of interest.

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