| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
|
FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online January 24, 2005 as doi:10.1096/fj.04-2674fje. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Nestlé Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland;
Center for Integrative Genomics, Université de Lausanne, Lausanne, Switzerland;
Lipomics Technologies, Inc., West Sacramento, California, USA; and;
Department of Food Science and Technology, University of California, Davis, California, USA
1Correspondence: Nestlé Purina Pet Care, Mail Zone 11T, Number One Checkerboard Square, St. Louis, Missouri 63164, USA. E-mail: mrsci68{at}yahoo.com
SPECIFIC AIMS
The aim of this study was to define the comprehensive effects of feeding an arachidonate-enriched (FUNGAL) oil and an eicosapentaenoic (EPA)/docosahexaenoic (DHA) -enriched (FISH) oil on hepatic lipid metabolism and gene expression, and to determine whether a combination (FUNGAL+FISH) of these two oils produces a response different from their individual effects.
PRINCIPAL FINDINGS
1. Comprehensive and quantitative lipid analysis identified a differential metabolism for the experimental diets and indicated that FUNGAL diet-mediated changes were not blocked by the concomitant feeding of the FISH diet
After the long-term consumption (57 days) of the control, FUNGAL, FISH, or the FUNGAL+FISH diets, quantitative analysis of the murine hepatic and hippocampal phospholipid (PL) profiles revealed differential responses both between and within the two organs. The hippocampal PL analysis demonstrated that this organ was more resistant to the experimental diets [i.e., no statistical differences in either the quantities or fatty acyl composition of cardiolipin (CL), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol/phosphatidylserine (PI/PS)]. In contrast, the liver PL profile revealed differential responses to the various diets. Diets supplemented with 1.1% arachidonate-enriched (FUNGAL) oil (consumed alone or in combination with the fish oil) resulted in a distinct clustering pattern for PC, PE, and PI/PS, as depicted in Fig. 1
. Subsequent decomposition of the data indicated that the clustering pattern arose due to quantitative differences for the following fatty acyl moieties: 16:0 (PA), 16:1 (PO), 18:0 (SA), 18:2 (LA), 20:4 (AA), and 22:6 (DHA). Whereas feeding the FISH diet alone did not result in a significant remodeling of hepatic PL species, mice consuming the FUNGAL+FISH diet produced a similar clustering profile as the FUNGAL diet alone (Fig. 1)
, indicating that the addition of an equivalent quantity of FISH did not attenuate the FUNGAL-induced phospholipid acyl restructuring.
|
2. Quantitative analysis of 40 different fatty acid species in CL, PC, PE, and PI/PS revealed that desaturation events were down-regulated by the FUNGAL diet
Simultaneous examination of 40 unique fatty acid species revealed the differential incorporation of these fatty acids into hepatic PL species. Whereas CL-acyl composition was not significantly modulated by the various diets, the remaining PL classes were enriched with saturated fatty acid species. Products of 
9 desaturation, calculated from the ratio of both 16:1/16:0 and 18:1/18:0, decreased in PL of mice fed the FUNGAL diet, as increases in 16:0 of 45% and 106% and increases in 18:0 of 60% and 63% were observed in mice fed the FUNGAL and FUNGAL+FISH diets, respectively (Fig. 2
). The FISH-supplemented diet did not yield a similar PL-enrichment in saturated fatty acids nor did it modulate the FUNGAL diet effects when fed together.
|
3. Comprehensive analysis of hepatic gene expression in mice fed the FUNGAL diet identified a gene network similar to that found in mice lacking the stearoyl CoA desaturase 1 (Scd1) gene
Gene expression was monitored by microarray technology and differentially expressed genes (experimental diet vs. control) were identified using a global error assessment model (P<0.01).
Mice lacking the Scd1 gene were characterized by a gene expression profile indicating increased ß-oxidation and decreased fatty acid synthesis. We found that Scd1 expression was significantly suppressed 1.1- and 1.8-fold by the FUNGAL diet and FUNGAL+FISH diet, respectively. The decreased expression of Scd1 was confirmed by semiquantitative real time PCR. Analyzing global gene expression in mice fed the FUNGAL diet revealed a similar profile (increased ß-oxidation and decreased fatty acid synthesis). Key genes involved in the biosynthesis of hepatic PC were significantly regulated in mice fed the FUNGAL diet. Glycerol-3-phosphate acyltransferase (Gpat/Gpam) and choline kinase (Chk) were down-regulated 1.7- and 2.2-fold by the FUNGAL diet alone and 2.3- and 2.2-fold by the FUNGAL+FISH diet, respectively. No significant differences in the expression of the aforementioned genes were observed in the livers of mice fed the FISH-supplemented diet.
CONCLUSIONS AND SIGNIFICANCE
The dietary supplementation of AA and EPA/DHA each regulate hepatic gene expression and lipid metabolism, but in different ways and these separate effects are not blocked when consumed together. Although lipid metabolite and gene expression analyses revealed molecular targets (both unique and shared) for each PUFA, the exploitation of a comprehensive integrated approach identified a previously unrecognized mechanism of action for AA. The hepatic glycerolipid profile after consumption of the FUNGAL diet (alone or in combination) was significantly modulated. The FUNGAL diet significantly decreased Scd1 gene expression and activity, resulting in significant differences in the fatty acid composition of several PL species.
The functions of dietary PUFA are not well understood and considerable debate surrounds whether they should be added to human foods, and in particular to infant formula. Previously published works highlight the complexity of PUFA metabolism and the scientific community’s perseverance to attribute biological functions to AA and EPA/DHA. The combination of gene expression and lipid profiling used in this work revealed that AA and EPA/DHA modulate various aspects of hepatic PL metabolism uniquely. More specifically, the present work demonstrates that the consumption of AA-enriched diets modulate the fatty acid content of hepatic PLs. Carefully designed experimental diets, in addition to an integrative metabolism approach, have identified an unrecognized and unique mechanism of action for AA in the regulation of lipid metabolism. The metabolic and genomic profile identified resembles that of the obesity-resistant SCD1–/– mouse developed by Prof. J. Natambi, revealing that AA has a fundamentally important role in the diet that is neither duplicated nor attenuated by the presence of EPA/DHA.
|
FOOTNOTES
To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.04-2674fje;
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
