Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI

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Abstract

Background/Objectives

Excessive infant weight gain in the first 6-months of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FA) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased 3-fold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBC) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2-weeks and 4-months postpartum.

Subjects/Methods

Forty-eight infants from normal-weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2-weeks) or established (4-months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry.

Results

In transitional and established HM, DHA was lower ( P=0.008; 0.005) and the AA/DHA+EPA ratio was higher ( P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy BMI and AA/ DHA+EPA ratios in transitional and established HM were moderately correlated ( P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile ( P=0.019). The amount of changes in infant fat mass and % body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010).

Conclusions

Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4-months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

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Most cited references 40

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Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c.

P. Ciraolo, Clinton Joiner, Lorraine P. Smith … (2008)

Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R(2) = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.

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Infant Feeding Practices Study II: study methods.

Sara B. Fein, Judith Labiner-Wolfe, Katherine Shealy … (2008)

Our goal is to describe the methods used in the Infant Feeding Practices Study II (IFPS II), a study of infant feeding and care practices throughout the first year of life. Survey topics included breastfeeding, formula and complementary feeding, infant health, breast-pump use, food allergies, sleeping arrangements, mother's employment, and child care arrangements. In addition, mothers' dietary intake was measured prenatally and postnatally. The IFPS II sample was drawn from a nationally distributed consumer opinion panel of 500,000 households. All questionnaires were administered by mail, 1 prenatally and 10 postpartum. Qualifying criteria were used to achieve the sample goals of mothers of healthy term and late preterm singleton infants. In addition to the questionnaires about the infants, women were sent a diet-assessment questionnaire prenatally and at approximately 4 months after delivery; this questionnaire was also sent to members of a comparison group who were neither pregnant nor postpartum. A sample of 4902 pregnant women began the study, and approximately 2000 continued through their infant's first year. Response rates ranged from 63% to 87% for the different questionnaires. Compared with adult mothers of singletons from the nationally representative sample of the National Survey of Family Growth, IFPS II participants had a higher mean education level; were older; were more likely to be middle income, white, and employed; were less likely to smoke; and had fewer other children. Compared with women who participated in the National Immunization Survey who gave birth in 2004, IFPS II mothers were more likely to breastfeed and to breastfeed longer. The IFPS II provides a valuable database because of its large sample size, the frequency of its questionnaires, and its wide coverage of issues salient to infant feeding.

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Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity

Anita R Alvheim, Marian K Malde, Douglas Osei-Hyiaman … (2012)

Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) is the ω-6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. LA was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the United States during the 20th century. Mice were fed diets containing 1 en% LA, 8 en% LA, and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium-fat diets (35 en% fat) and high-fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA-phospholipids (PL) in liver and erythrocytes, tripled 2-AG + 1-AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA-PL by adding 1 en% long-chain ω-3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2-AG + 1-AG and AEA resulting in the development of diet-induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA-PL pool and normalize endocannabinoid tone.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101256108

Journal ID (pubmed-jr-id): 32579

Journal ID (nlm-ta): Int J Obes (Lond)

Journal ID (iso-abbrev): Int J Obes (Lond)

Title: International journal of obesity (2005)

ISSN (Print): 0307-0565

ISSN (Electronic): 1476-5497

Publication date Nihms-submitted: 5 November 2016

Publication date (Electronic): 23 November 2016

Publication date (Print): April 2017

Publication date PMC-release: 23 May 2017

Volume: 41

Issue: 4

Pages: 510-517

Affiliations

[1 ]Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO

[2 ]Department of Pediatrics, Section of Nutrition, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO

[3 ]Department of Pediatrics, Section of Neonatology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO

[4 ]Department of Pediatrics, Section of College of Nursing, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO

[5 ]Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO

Author notes

Corresponding Author: Michael C. Rudolph, University of Colorado Denver, Center for Human Nutrition | Division of Endocrinology, Metabolism and Diabetes, Mail Stop F-8305; RC1 North, 12800 E. 19th Avenue P18-5402M, Aurora, CO 80045, michael.rudolph@ 123456ucdenver.edu , Phone: 303-724-6878, Fax: 303-724-3031

[*]

Denotes co-first authors; these authors contributed equally to this work.

[**]

Denotes co-senior authors; these authors contributed equally to this work.

[6]

Present address: Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL 32608

Article

Manuscript ID: NIHMS827237

DOI: 10.1038/ijo.2016.211

PMC ID: 5380514

PubMed ID: 27876761

SO-VID: db44a745-ad60-4aeb-aa50-7b481138d79c

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Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI

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Abstract

Background/Objectives

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Most cited references 40

Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c.

Infant Feeding Practices Study II: study methods.

Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity

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