PUBLICATION
Microsomal Triglyceride Transfer Protein Is Required for Yolk Lipid Utilization and Absorption of Dietary Lipids in Zebrafish Larvae
- Authors
- Schlegel, A., and Stainier, D.Y.
- ID
- ZDB-PUB-061229-10
- Date
- 2006
- Source
- Biochemistry 45(51): 15179-15187 (Journal)
- Registered Authors
- Schlegel, Amnon, Stainier, Didier
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Carrier Proteins/administration & dosage
- Carrier Proteins/genetics
- Carrier Proteins/physiology*
- Cell Line, Tumor
- Dietary Fats/metabolism*
- Egg Yolk/metabolism*
- Humans
- Intestinal Absorption/genetics
- Intestinal Absorption/physiology
- Larva/genetics
- Larva/metabolism
- Larva/physiology
- Lipid Metabolism/genetics
- Lipoproteins, LDL/metabolism
- Microsomes/metabolism
- Triglycerides/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish/physiology
- PubMed
- 17176039 Full text @ Biochemistry
Citation
Schlegel, A., and Stainier, D.Y. (2006) Microsomal Triglyceride Transfer Protein Is Required for Yolk Lipid Utilization and Absorption of Dietary Lipids in Zebrafish Larvae. Biochemistry. 45(51):15179-15187.
Abstract
Although the absorption, transport, and catabolism of dietary lipids have been studied extensively in great detail in mammals and other vertebrates, a tractable genetic system for identifying novel genes involved in these physiologic processes is not available. To establish such a model, we monitored neutral lipid by staining fixed zebrafish larvae with oil red o (ORO). The head structures, heart, vasculature, and swim bladder stained with ORO until the yolk was consumed 6 days after fertilization (6 dpf). Thereafter, the heart and vasculature no longer had stainable neutral lipids. Following a high-fat meal, ORO stained the intestine and vasculature of 6 dpf larvae, and whole-larval triacylglycerol (TAG) and apolipoprotein B levels increased. Levels of microsomal triglyceride transfer protein (Mtp), the protein responsible for packaging TAG and betalipoproteins into lipoprotein particles, were unchanged by feeding. Since the developing zebrafish embryo expresses mtp in the yolk cell layer, liver, and intestine, we determined the effect of targeted knockdown of Mtp expression using an antisense morpholino oligonucleotide approach (Mtp MO) on the transport of yolk and dietary lipids. Mtp MO injection led to loss of Mtp expression and of lipid staining in the vasculature, heart, and head structures. Mtp MO-injected larvae were smaller than age-matched, uninjected larvae, consumed very little yolk, and did not absorb dietary neutral lipids; however, they absorbed a short chain fatty acid that does not require Mtp for transport. Importantly, the vasculature appeared unaffected in Mtp MO-injected larvae. These studies indicate that zebrafish larvae are suitable for genetic studies of lipid transport and metabolism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping