Abstract
Background:
Bariatric surgery affects lipid levels; however, no comparison of the effects of Roux-en-Y gastric bypass surgery (RYGB) versus vertical sleeve gastrectomy (VSG) on serum fatty acid levels exists in the current literature. The present post-hoc study describes the effects of RYGB and VSG on serum fatty acid levels at 6 months and 18 months post treatment, compared to a control group.
Methods:
The study participants, all of whom were women, had blood drawn at baseline, 6 months, and 18 months after treatment. Serum fatty acid data were available for 57 participants at baseline, 57 participants at 6 months, and 43 participants at 18 months post-treatment.
Results:
Compared to baseline, serum non-esterified fatty acids (NEFA) levels were significantly higher at 6 and 18 months in the VSG group compared to the RYGB group. In the RYGB group, all three of the measured saturated fatty acids (SFAs), two of the three measured monounsaturated fatty acids (MUFAs), and two of the three measured polyunsaturated fatty acids (PUFAs) were decreased at 6 and 18 months compared to baseline, although not all of these changes were significant compared to the control and VSG groups. On the other hand, one of the three MUFAs and two of the three PUFAs were increased at 6 and 18 months in the VSG group, although these changes were not all significant compared to the control and RYGB groups. Significant positive associations were noted between change in body mass index (BMI) and two of the SFAs and one of the MUFAs. Similarly, significant positive associations were noted between change in HOMA-IR and 3 of the measured fatty acids.
Conclusions:
At 6 and 18 months after VSG, a significant increase in NEFAs was seen, compared to RYGB. Reductions in all measured SFAs and most measured MUFAs and PUFAs at 6 and 18 months post RYGB were seen, although not all of these decreases were significant when compared to the control and VSG groups. Similarly, increases in most of the PUFAs at 6 and 18 months were observed after VSG, although not all of these changes were significant when compared to the other treatment groups. Changes in BMI and HOMA-IR were significantly associated with changes in some but not all fatty acids.
Keywords: obesity, gastric bypass surgery, sleeve gastrectomy, lipids, fatty acids
Introduction
Obese individuals who undergo bariatric surgery have improved cardiometabolic outcomes, and retrospective studies have demonstrated a decreased risk of mortality [1,2]. Possible factors underlying the reduction in mortality include diabetes remission and decreased rates of diabetes-associated microvascular and macrovascular complications [3]. Serum fatty acid levels, which can influence inflammation and low-density lipoprotein oxidation, represent a factor that could account for decreased cardiometabolic risk after bariatric surgery [4]. Some studies have suggested that replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) in the diet decreases incident coronary heart disease risk [5], and increased circulating plasma levels of certain PUFA species have been found to be associated with lower risk of incident cardiovascular disease (CVD) [6].
Bariatric surgery has been found to alter serum fatty acid levels [7]. Vertical sleeve gastrectomy (VSG) decreases gastric size, whereas biliopancreatic diversion with duodenal switch (BPDDS) and Roux-en-Y gastric bypass surgery (RYGB) both decrease gastric size and cause malabsorption of macronutrients [8]. After RYGB, reduced fat absorption as a result of both decreased fat intake and malabsorption have been noted [9]. Lin et al found that serum eicosapentaenoic (EPA) levels and the ratio of EPA to α-linolenic acid decreased at 3 months after BPDDS from baseline and remained significantly decreased at 12 months. Similarly, EPA levels and the ratio of EPA/arachidonic acid (AA) decreased 3 months after laparoscopic sleeve gastrectomy but increased at 12 months, although not back to baseline [7]. However, the current literature is limited in comparing the effects of VSG and RYGB on serum fatty acid levels.
The current study is a post-hoc analysis of data from a previously published prospective observational study of obese female participants who underwent either RYGB or VSG and were compared to a body mass index (BMI)-matched control group [10,11]. Alamuddin et al measured the effects of RYGB and VSG on body weight, BMI, insulin resistance and leptin, as well as gut hormone responses to a meal challenge at baseline and at 6 and 18 months after bariatric surgery. The primary aim of the current study is to compare changes in serum fatty acid levels at 6 months and 18 months post surgery from baseline between the control, RYGB, and VSG treatment groups.
Materials and Methods
Study population
The details of the parent study have been published previously [10,11]. Briefly, the study participants were women, age ≥ 18 years, with a BMI ≥ 40 kg/m2 (or ≥ 35 kg/m2 with significant co-morbid conditions). Individuals who were pregnant, lactating, or had a history of diabetes, recent substance abuse, weight loss medication use, or unstable psychiatric disease were excluded. The University of Pennsylvania Institutional Review Board approved the study (Clinical Trials registration number ). Participants undergoing surgery decided with their surgeon whether to undergo RYGB or VSG. Weight-matched controls agreed to maintain their baseline weight (within 5%) over the course of 18 months.
Serum fatty acid measurements
Blood was obtained from participants at baseline (within 4 weeks before surgery) and at 6 months and 18 months post surgery. Serum non-esterified fatty acids (NEFAs) were measured using enzymatic colorimetric assay [12], and total fatty acid concentrations were measured at the Metabolic Tracer Resource at the University of Pennsylvania. Heptadecanoic acid was added to each plasma sample as an internal standard. Lipids were extracted on ice using chloroform: methanol (2:1). The lipid extract was dried, saponified using 0.3N KOH-methanol and fatty acids derivatized to their fatty acid methyl esters (FAMEs). FAMEs were extracted into hexane and injected into an Agilent 7890A/5975 GC/MS run in electron ionization mode fitted with a DB-5MS column. Fatty acids were identified using known standards and normalized to the internal standard. The concentration of each fatty acid was determined using a standard curve. The following fatty acids were measured: NEFAs, SFAs (C14:0, C16:0, and C18:0), monounsaturated fatty acids (MUFAs) (C16:1, C18:1 n9, and C18:1 n7), and PUFAs (C18:2, C20:3, C20:4).
Statistical analyses
Linear mixed models with residual maximum likelihood were used to determine whether the control, VSG, and RYGB groups differed in change in fatty acids from baseline at month 6 and month 18. Unconditional models were used to determine the appropriate model shape (e.g., linear, quadratic, piece-wise) and variance-covariance structure based on model fit criteria (e.g., −2 log likelihood) [13]. Data modeled were change in fatty acid levels controlling for baseline levels of the fatty acid. Estimated changes in fatty acids from baseline were compared between groups using least squared means. Linear mixed models also were used to study associations between changes in fatty acids and changes in BMI and HOMA-IR. SPSS statistical software (version 25) was used for all analyses.
Results
Patient characteristics
Table 1 presents baseline characteristics of the participants. In the parent study, 68 participants completed baseline assessments, 64 participants completed 6 month assessments, and 51 participants completed the 18 month assessments. In the present study, fatty acid levels were available for 57 of the participants at baseline. Measurements were provided by 56 of these participants at month 6 and 41 participants at month 18. All 57 participants were included in the statistical analyses. Because baseline differences between at least two groups were observed for six of the fatty acids (Table 1), baseline levels were included as a covariate in all subsequent analyses.
Table 1:
Baseline characteristics
| Variable | Control (N=19) | VSG (N=17) | RYGB (N=21) | Total (N=57) |
|---|---|---|---|---|
| Age (years) | 35.7 (8.4) | 39.7 (8.4) | 35.6 (10.1) | 36.8 (9.1) |
| Race** | ||||
| Black | 15 (78.9%) | 12 (70.6%) | 8 (38.1%) | 35 (61.4%) |
| White | 3 (15.8%) | 4 (23.5%) | 13 (61.9%) | 21 (31.5%) |
| Other | 1 (5.3%) | 1 (5.9%) | 0 (0%) | 2 (3.6%) |
| Weight (kg) | 116.0 (14.8) | 117.8 (11.8) | 119.5 (12.8) | 117.8 (13.1) |
| BMI (kg/m2) | 43.3 (4.4) | 43.7 (4.2) | 44.6 (4.2) | 43.9 (4.2) |
| Triglycerides (mg/dL)* | 61.6 (24.2)a | 85.9 (32.6)ab | 90.3 (35.0)b | 79.3 (33.1) |
| Total cholesterol (mg/dL)* | 158.8 (21.3) | 168.8 (37.9) | 173.1 (41.7) | 167.0 (34.8) |
| Fasting glucose (mg/dL)* | 96.1 (10.0) | 99.5 (12.4) | 97.2 (8.4) | 97.5 (10.3) |
| Fasting insulin (μU/mL)* | 20.2 (2.8) | 17.2 (5.5) | 15.5 (6.7) | 17.4 (7.7) |
| HOMA-IR* | 5.0 (2.8) | 4.3 (1.6) | 3.7 (1.8) | 4.3 (2.2) |
| Non-esterified Fatty Acids | ||||
| Serum NEFA (mEq/L) | 0.54 (0.17) | 0.58 (0.17) | 0.59 (0.16) | 0.57 (0.17) |
| Saturated Fatty Acids | ||||
| C14:0 (μg/mL) | 7.1 (3.4)a | 7.5 (4.4)ab | 11.2 (5.6)b | 8.7 (4.9) |
| C16:0 (μg/mL) | 261.8 (62.8)a | 332.0 (58.7)b | 283.1 (56.5)a | 290.6 (64.9) |
| C18:0 (μg/mL) | 107.6 (22.4)a | 136.0 (24.5)b | 108.2 (25.1)a | 116.3 (26.9) |
| Monounsaturated Fatty Acids | ||||
| C16:1 (μg/mL) | 16.9 (8.5)a | 18.8 (6.4)a | 29.6 (12.8)b | 22.1 (11.3) |
| C18:1 n7 (μg/mL) | 19.0 (8.5) | 23.2 (9.6) | 24.4 (7.0) | 22.2 (8.5) |
| C18:1 n9 (μg/mL) | 173.2 (53.0)a | 220.6 (68.7)ab | 227.32 (56.4)b | 207.3 (63.1) |
| Polyunsaturated Fatty Acids | ||||
| C18:2 (μg/mL) | 300.5 (84.0) | 321.7 (97.2) | 328.4 (86.2) | 317.1 (88.1) |
| C20:3 (μg/mL) | 9.8 (5.8)a | 9.6 (6.5)a | 15.7 (5.3)b | 11.9 (6.4) |
| C20:4 (μg/mL) | 66.4 (28.6) | 66.0 (37.8) | 85.3 (25.1) | 73.3 (31.4) |
Values shown are N (%) or means (standard deviation). Note: BMI = body mass index; HOMA-IR = homeostatic model assessment of insulin resistance. Significant differences (P < 0.05) between treatment groups are marked using superscripts. (Values with different superscripts (a vs b) differ significantly from each other. Values that share a superscript do not differ significantly.)
Sample size is 56 for triglycerides and cholesterol (n = 19, n = 16, and n = 21, respectively), 55 for glucose and leptin (n = 18, n = 16, and n = 21, respectively), and 54 for insulin and HOMA-IR (n = 17, n = 16, and n = 21, respectively).
The distribution of black/non-black races differed significantly among the groups (P = 0.019).
NEFAs
Table 2 shows the mean changes in baseline fatty acids at months 6 and 18 for each group. There were larger increases in NEFAs from baseline at both 6 (P = 0.044) and 18 months (P = 0.005) in the VSG group, compared to the RYGB group. The VSG group also had larger increases in NEFAs at month 6 relative to the control group (p = 0.046).
Table 2.
Estimated mean changes in baseline fatty acids at months 6 and 18 in the intention-to-treat population (N=57).
| Variable | Control (N = 19) |
VSG (N = 17) |
RYGB (N = 21) |
P value | ||
|---|---|---|---|---|---|---|
| Control vs. VSG | Control vs. RYGB | VSG vs. RYGB | ||||
| Non-esterified Fatty Acids | ||||||
| Change in Serum NEFA (mEq/L) | ||||||
| Month 6 | −0.003 ± 0.04 | +0.11 ± 0.04 | +0.001 ± 0.04 | 0.046 | 0.951 | 0.044 |
| Month 18 | +0.06 ± 0.05 | +0.19 ± 0.05 | +0.01 ± 0.04 | 0.055 | 0.413 | 0.005 |
| Saturated Fatty Acids | ||||||
| Change in C14:0 (μg/mL) | ||||||
| Month 6 | −0.7 ± 0.8 | −4.3 ± 0.8 | −2.5 ± 0.8 | 0.003 | 0.134 | 0.130 |
| Month 18 | −0.1 ± 0.9 | −0.8 ± 0.9 | −0.3 ± 0.8 | 0.588 | 0.876 | 0.708 |
| Change in C16:0 (μg/mL) | ||||||
| Month 6 | −7.5 ± 12.5 | −4.8 ± 13.3 | −50.8 ± 11.2 | 0.890 | 0.011 | 0.011 |
| Month 18 | −17.0 ± 13.7 | −4.0 ± 14.4 | −39.6 ± 12.2 | 0.538 | 0.225 | 0.062 |
| Change in C18:0 (μg/mL) | ||||||
| Month 6 | −0.4 ± 6.1 | −13.1 ± 6.7 | −30.8 ± 5.6 | 0.186 | <0.001 | 0.056 |
| Month 18 | −0.7 ± 6.6 | +14.6 ± 7.3 | −21.8 ± 6.0 | 0.142 | 0.018 | <0.001 |
| Monounsaturated Fatty Acids | ||||||
| Change in C16:1 (μg/mL) | ||||||
| Month 6 | −1.3 ± 2.1 | −7.2 ± 2.1 | −6.3 ± 2.1 | 0.046 | 0.114 | 0.766 |
| Month 18 | −0.1 ± 2.2 | −5.6 ± 2.2 | −3.6 ± 2.2 | 0.076 | 0.301 | 0.546 |
| Change in C18:1 n7 (μg/mL) | ||||||
| Month 6 | −2.5 ± 1.8 | +5.5 ± 1.8 | −2.3 ± 1.6 | 0.002 | 0.930 | 0.002 |
| Month 18 | +0.7 ± 1.9 | −0.4 ± 1.9 | −4.3 ± 1.7 | 0.696 | 0.062 | 0.134 |
| Change in C18:1 n9 (μg/mL) | ||||||
| Month 6 | −19.2 ± 11.2 | +21.9 ± 11.2 | −16.6 ± 10.2 | 0.013 | 0.872 | 0.012 |
| Month 18 | −26.1 ± 12.1 | +7.0 ± 11.9 | +4.3 ± 11.2 | 0.060 | 0.081 | 0.867 |
| Polyunsaturated Fatty Acids | ||||||
| Change in C18:2 (μg/mL) | ||||||
| Month 6 | −29.7 ± 13.9 | +10.0 ± 14.2 | −63.9 ± 12.8 | 0.050 | 0.075 | <0.001 |
| Month 18 | −39.3 ± 15.3 | +47.9 ± 15.3 | −18.0 ± 14.4 | <0.001 | 0.325 | 0.002 |
| Change in C20:3 (μg/mL) | ||||||
| Month 6 | −1.5 ± 1.0 | −4.3 ± 1.1 | −4.4 ± 1.0 | 0.063 | 0.058 | 0.933 |
| Month 18 | −1.1 ± 1.1 | +1.7 ± 1.1 | +0.6 ± 1.2 | 0.084 | 0.347 | 0.497 |
| Change in C20:4 (μg/mL) | ||||||
| Month 6 | −5.2 ± 5.0 | +2.3 ± 5.1 | −10.7 ± 4.7 | 0.291 | 0.430 | 0.070 |
| Month 18 | −9.7 ± 5.3 | +7.9 ± 5.4 | −6.4 ± 5.1 | 0.022 | 0.655 | 0.062 |
Values shown are estimated marginal means (± SE) for the intention-to-treat population (N = 57), adjusted for baseline levels of the fatty acid.
SFAs
The RYGB group had significant decreases relative to baseline in all three saturated fatty acids at both month 6 and month 18 (with exception of C14:0 at month 18, P = 0.733) and had larger decreases in SFAs than the other groups at several time points. In particular, at 6 months, RYGB had larger decreases in C16:0 compared to the control group (P = 0.011) and the VSG group (P = 0.011) and in C18:0 compared to the control group (P < 0.001). At 18 months, decreases in C18:0 were larger with RYGB compared to both the control group (P = 0.018) and the VSG group (P < 0.001).
In the VSG group, there were larger decreases from baseline in C14:0 at 6 months compared to the control group (p = 0.003), but this difference did not persist at 18 months.
MUFAs
At month 6, the VSG group showed a different pattern of change in MUFAs relative to the other two treatment groups. VSG had larger initial decreases in C16:1 (P = 0.002 for change relative to baseline) than the control group, which did not differ from RYGB. However, both C18:1 n7 and C18:1 n9 appeared to increased in VSG at month 6 (P = 0.003 and P = 0.054 for changes relative to baseline, respectively). The changes in both C18:1 n7 and C18:1 n9 in VSG differed significantly from the control group and the RYGB group at month 6. Levels of C18:1 n7 and C18:1 n9 in VSG were not significantly different from baseline at month 18, and there were no significant differences in change in any of the MUFAs among the groups at that time.
PUFAs
The pattern of change in PUFAs was also distinct for VSG at some time points. The VSG group had a non-significant increase in C18:2 at month 6 (P = 0.484) whereas the control and RYGB groups decreased significantly in C18:2 (P = 0.36 and P < 0.001, respectively, compared to baseline). The VSG and RYGB groups differed in change in C18:2 at that time (P < 0.001). By month 18, C18:2 had increased significantly for VSG participants relative to baseline (P = 0.002), and this change differed significantly from the decreases seen in both the control and RYGB group. The VSG group also increased in C20:3 and C20:4 at most time points, but compared to the other treatment groups, these changes were not statistically significant. The only difference among the groups in these two PUFAs occurred between VSG (increased) and control (decreased) in C20:4 at month 18.
Relation of fatty acids and BMI
No significant association was observed between change in NEFAs and change in BMI (Table 3). Significant direct associations were seen between changes in two SFAs, C16:0 and C18:0, and one MUFA, C16:1, and change in BMI (P = 0.002, P < 0.001, and P < 0.001, respectively).
Table 3:
Associations between changes over time in BMI and HOMA-IR and changes in fatty acids in the intention-to-treat population.
| Change in Variable | Change in BMI (N=57) | Change in HOMA-IR (N=54) |
|---|---|---|
| Non-esterified Fatty Acids | ||
| Serum NEFA (mEq/L) | −0.0002 ± 0.005 | 0.006 ± 0.01 |
| Saturated Fatty Acids | ||
| C14:0 (μg/mL) | 0.13 ± 0.09 | 0.61 ± 0.16*** |
| C16:0 (μg/mL) | 3.89 ± 1.23** | 5.20 ± 2.83° |
| C18:0 (μg/mL) | 2.08 ± 0.57*** | 2.41 ± 1.33° |
| Monounsaturated Fatty Acids | ||
| C16:1 (μg/mL) | 0.71 ± 0.18*** | 1.16 ± 0.34** |
| C18:1 n7 (μg/mL) | 0.33 ± 0.18° | −0.09 ± 0.41 |
| C18:1 n9 (μg/mL) | 0.89 ± 1.18 | 2.18 ± 2.49 |
| Polyunsaturated Fatty Acids | ||
| C18:2 (μg/mL) | 1.06 ± 1.62 | −0.89 ± 3.53 |
| C20:3 (μg/mL) | 0.12 ± 0.11 | 0.48 ± 0.23* |
| C20:4 (μg/mL) | 0.60 ± 0.49 | 0.70 ± 1.09 |
Values shown are b ± standard error for the relationship between change in the variables over time during the 18 month follow-up period. Note: BMI = body mass index; HOMA-IR = homeostatic model assessment of insulin resistance;
P < 0.10;
P < 0.05;
P < 0.01;
P < 0.001.
Sample size for each analysis varies due to differences in available data at baseline.
Relation of fatty acids and HOMA-IR
No significant association was observed between change in NEFAs and change in HOMA-IR (Table 3). Significant direct associations were seen between changes in one SFA, C14:0, one MUFA, C16:1, and one PUFA, C20:3, and change in HOMA-IR (P < 0.001, P = 0.001, and P = 0.036, respectively).
Conclusion
This post-hoc analyses of serum fatty acids post-bariatric surgery showed different patterns of fatty acid levels between a control group, a RYGB group and a VSG group. One finding was that NEFAs were significantly more increased at both 6 and 18 months post baseline in the VSG group, compared to the RYGB group.
Both significant and non-significant decreases in several of the measured fatty acids were seen at 6 and 18 months in the RYGB group and the control group, whereas increases in some of the fatty acids were seen in at 6 and 18 months in the VSG group.
Lin et al noted that EPA and EPA/AA levels tended to move towards baseline at 1 year post surgery in participants who had undergone sleeve gastrectomy. However, in participants who had undergone BPDDS, EPA and EPA/AA levels were decreased at both 3 months and at 1 year compared to baseline. The authors postulated that this difference was because BPDDS, unlike sleeve gastrectomy, causes malabsorption [7]. Similar to BPDDS, malabsorption is seen after RYGB and may explain some of the decreases in fatty acids that were noted in this group in this study, although this was not seen with all of the measured fatty acids. In another study by Wijayatunga et al, two SFAs, C14:0 and C18:0, significantly increased and NEFAs significantly decreased at 6 months compared to baseline in patients who had undergone RYGB [14]. However, this study did not have a control group and had a sample size of 8 participants.
Decreased food consumption may also play a role in the changes in serum fatty acids seen after bariatric surgery. Decreases in macronutrient, including lipids, and micronutrient intake, as measured by food records, have been observed in the short-term after RYBG [15]. Of note, in a study of long-term follow-up of dietary intake of individuals who underwent either RYGB or VSG, no difference in amount of energy intake from lipids at 6 and 12 months after surgery compared to baseline was noted between the two groups, and no differences were noted at 6 or 12 months compared to baseline in SFA, MUFA, and PUFA intake between the two groups [16].
Fatty acids have been implicated in regulating glucose homeostasis in obese individuals [17]. We detected significant direct associations between change in BMI and 3 of the 10 measured fatty acids. Similarly, we found significant direct associations between change in HOMA-IR and 3 fatty acids. In a study of Caucasian female participants, Honka et al found significant decreases in BMI, pancreatic fatty acid uptake, and fasting glucose and insulin levels at 6 months post RYGB surgery compared to baseline; however, there was no significant change in free fatty acid levels [18]. In contrast, Nemati et al. reported that of participants who underwent either RYGB, VSG, or a very low calorie diet, there was a small but significant positive correlation between total insulin secretion during an oral glucose tolerance test and serum C18:2 levels, at baseline and 3 days post-treatment. Moreover, the C18:0 levels and ratio of MUFA/PUFA and unsaturated/saturated fatty acids had a weak but significant positive correlation with HOMA-IR [19]. We did not find a significant association between change in HOMA-IR and change in C18:0 in our study. These differences in findings may be attributed to measurements being obtained at different times post-surgery (i.e. days vs. months).
Bariatric surgery is associated with improvements in CVD risk factors such as obesity, hypertension, and type 2 diabetes, and some evidence shows that bariatric surgery is associated with decreased risk of myocardial infarction [20]. Both increased EPA (C20:5 n3) and EPA to AA (C20:4) ratio have been associated with decreased CVD [21]. C20:5 n3 was not evaluated in the present study, but C20:4 was found to be significantly increased in VSG participants compared to controls at 18 months. However, this was not noted in RYGB participants.
The strengths of the present study include a relatively long follow-up period of 18 months and comparison to a control group. A limitation is that the participants were not randomized to treatment groups.
In summary, we found that significant increases in NEFAs at 6 and 18 months after VSG compared to RYGB. In addition, we observed decreases in SFAs at 6 and 18 months after RYGB and increases in one of three MUFAs and two of three PUFAs at 18 months after VSG.
Funding:
This research was supported by grant number R01-DK085615 (TW), and the Bloomberg Professorship.
Footnotes
Conflict of Interest: SS, RSA, FA, JM and NA have nothing to declare. TAW reports serving on advisory boards for Novo Nordisk and Weight Watchers International. NA reports receiving reimbursement for consulting for Novo Nordisk.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
References
- 1.Arterburn DE, Olsen MK, Smith VA, Livingston EH, Van Scoyoc L, Yancy WS Jr., Eid G, Weidenbacher H, Maciejewski ML. Association between bariatric surgery and long-term survival. JAMA 2015;313:62–70. [DOI] [PubMed] [Google Scholar]
- 2.Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [DOI] [PubMed] [Google Scholar]
- 3.Sjostrom L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden A, Bouchard C, Carlsson B, Karason K, Lonroth H, Naslund I, Sjostrom E, Taube M, Wedel H, Svensson PA, Sjoholm K, Carlsson LM. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA 2014;311:2297–304. [DOI] [PubMed] [Google Scholar]
- 4.Kaikkonen JE, Kresanov P, Ahotupa M, Jula A, Mikkila V, Viikari JS, Kahonen M, Lehtimaki T, Raitakari OT. High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study. Free Radic Res 2014;48:420–6. [DOI] [PubMed] [Google Scholar]
- 5.Michas G, Micha R, Zampelas A. Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle. Atherosclerosis 2014;234:320–8. [DOI] [PubMed] [Google Scholar]
- 6.de Oliveira Otto MC, Wu JH, Baylin A, Vaidya D, Rich SS, Tsai MY, Jacobs DR Jr., Mozaffarian D. Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2013;2:e000506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Lin C, Vage V, Mjos SA, Kvalheim OM. Changes in Serum Fatty Acid Levels During the First Year After Bariatric Surgery. Obes Surg 2016;26:1735–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Fruhbeck G. Bariatric and metabolic surgery: a shift in eligibility and success criteria. Nat Rev Endocrinol 2015;11:465–77. [DOI] [PubMed] [Google Scholar]
- 9.Odstrcil EA, Martinez JG, Santa Ana CA, Xue B, Schneider RE, Steffer KJ, Porter JL, Asplin J, Kuhn JA, Fordtran JS. The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass. The American journal of clinical nutrition 2010;92:704–13. [DOI] [PubMed] [Google Scholar]
- 10.Faulconbridge LF, Ruparel K, Loughead J, Allison KC, Hesson LA, Fabricatore AN, Rochette A, Ritter S, Hopson RD, Sarwer DB, Williams NN, Geliebter A, Gur RC, Wadden TA. Changes in neural responsivity to highly palatable foods following roux-en-Y gastric bypass, sleeve gastrectomy, or weight stability: An fMRI study. Obesity (Silver Spring) 2016;24:1054–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Alamuddin N, Vetter ML, Ahima RS, Hesson L, Ritter S, Minnick A, Faulconbridge LF, Allison KC, Sarwer DB, Chittams J, Williams NN, Hayes MR, Loughead JW, Gur R, Wadden TA. Changes in Fasting and Prandial Gut and Adiposity Hormones Following Vertical Sleeve Gastrectomy or Roux-en-Y-Gastric Bypass: an 18-Month Prospective Study. Obes Surg 2017;27:1563–72. [DOI] [PubMed] [Google Scholar]
- 12.Imai Y, Boyle S, Varela GM, Caron E, Yin X, Dhir R, Dhir R, Graham MJ, Ahima RS. Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid metabolism and gene expression. Physiol Genomics 2012;44:1125–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Tasca GA, Gallop R. Multilevel modeling of longitudinal data for psychotherapy researchers: I. The basics. Psychother Res 2009;19:429–37. [DOI] [PubMed] [Google Scholar]
- 14.Wijayatunga NN, Sams VG, Dawson JA, Mancini ML, Mancini GJ, Moustaid-Moussa N. Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity- A prospective exploratory pilot study. Diabetes Metab Res Rev 2018:e3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Custodio Afonso Rocha V, Ramos de Arvelos L, Pereira Felix G, Nogueira Prado de Souza D, Bernardino Neto M, Santos Resende E, Penha-Silva N. Evolution of nutritional, hematologic and biochemical changes in obese women during 8 weeks after Roux-en-Y gastric bypasss. Nutr Hosp 2012;27:1134–40. [DOI] [PubMed] [Google Scholar]
- 16.Moize V, Andreu A, Flores L, Torres F, Ibarzabal A, Delgado S, Lacy A, Rodriguez L, Vidal J. Long-term dietary intake and nutritional deficiencies following sleeve gastrectomy or Roux-En-Y gastric bypass in a mediterranean population. J Acad Nutr Diet 2013;113:400–10. [DOI] [PubMed] [Google Scholar]
- 17.Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes 2003;111:121–4. [DOI] [PubMed] [Google Scholar]
- 18.Honka H, Koffert J, Hannukainen JC, Tuulari JJ, Karlsson HK, Immonen H, Oikonen V, Tolvanen T, Soinio M, Salminen P, Kudomi N, Mari A, Iozzo P, Nuutila P. The effects of bariatric surgery on pancreatic lipid metabolism and blood flow. J Clin Endocrinol Metab 2015;100:2015–23. [DOI] [PubMed] [Google Scholar]
- 19.Nemati R, Lu J, Tura A, Smith G, Murphy R. Acute Changes in Non-esterified Fatty Acids in Patients with Type 2 Diabetes Receiving Bariatric Surgery. Obes Surg 2017;27:649–56. [DOI] [PubMed] [Google Scholar]
- 20.Beamish AJ, Olbers T, Kelly AS, Inge TH. Cardiovascular effects of bariatric surgery. Nat Rev Cardiol 2016;13:730–43. [DOI] [PubMed] [Google Scholar]
- 21.Ohnishi H, Saito Y. Eicosapentaenoic acid (EPA) reduces cardiovascular events: relationship with the EPA/arachidonic acid ratio. J Atheroscler Thromb 2013;20:861–77. [DOI] [PubMed] [Google Scholar]