TAG Synthesis and DGAT1 Deficiency

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Questions and Answers

What method was used to measure plasma triacylglycerol quantities?

Ultracentrifugation

Agarose gel electrophoresis

Reversed-phase liquid chromatography

Colorimetric assay (correct)

What was the primary diet component mixed with retinol palmitate for fasted mice?

Corn oil (correct)

Soybean oil

Olive oil

Sunflower oil

Which specific fatty acid analog was used in the study?

Stearic acid

Palmitic acid

[125I]BMIPP (correct)

Linoleic acid

What were the observed plasma triacylglycerol concentrations after an intragastric oil bolus in wild-type mice compared to Dgat1-/- mice?

Significantly higher in wild-type mice Signup and view all the answers

What was the result of the ultracentrifugation in wild-type plasma samples?

Visible chylomicrons were present Signup and view all the answers

In gel electrophoresis, which lipoproteins are identified at the corresponding bands?

HDL in the ⍺ band Signup and view all the answers

Which technique was used to analyze plasma retinol levels?

Reversed-phase liquid chromatography Signup and view all the answers

What was measured to assess the absorption effectiveness of BMIPP by the intestines of mice?

[125I]BMIPP radioactivity Signup and view all the answers

What was the observed concentration of chylomicrons in Dgat1-/- mice compared to wild-type mice?

Approximately 60% lower Signup and view all the answers

How much lower were the plasma levels of BMIPP in Dgat1-/- mice compared to wild-type mice?

75% lower Signup and view all the answers

What method was used to analyze intestinal tissues for electron microscopy?

Stained with Osmium tetroxide Signup and view all the answers

What was the primary reason for lipid accumulation in the enterocytes of Dgat1-/- mice?

Depleted TAG absorption and chylomicron synthesis Signup and view all the answers

What diet did the Dgat1-/- mice need to be fed to see lipid accumulation in enterocytes?

High-fat diet Signup and view all the answers

What was the outcome in Dgat1-/- mice when fed a diet of rodent chow?

Lipid droplets did not accumulate Signup and view all the answers

What procedure was used for mRNA purification from the intestinal mucosa?

RNA STAT60 method Signup and view all the answers

What happens to DGAT-/- mice when fed a high-fat diet?

They become overwhelmed Signup and view all the answers

What role does DGAT1 play in triacylglycerol absorption?

It has no effect on triacylglycerol absorption. Signup and view all the answers

What was observed in Dgat1-/- mice when fed a high fat diet?

They accumulated neutral-lipid droplets in enterocytes. Signup and view all the answers

How much lower was DGAT activity in more distal regions of the small intestine?

50% lower than in proximal regions. Signup and view all the answers

Which enzymes help compensate for the lack of DGAT1 in intestinal TAG synthesis?

Both DGAT2 and DAG transacylase Signup and view all the answers

What percentage of chylomicrons is primarily composed of triacylglycerols (TAGs)?

90% Signup and view all the answers

How is DGAT2 expression characterized in different segments of the small intestine?

Higher in proximal regions than in distal regions. Signup and view all the answers

What role does diacylglycerol acyltransferase (DGAT) play in the metabolism of fats?

It converts diacylglycerol into triacylglycerol. Signup and view all the answers

What happens to DGAT activity levels in Dgat1-/- mice compared to WT mice?

It is at 10-15% of the levels in WT mice. Signup and view all the answers

Which enzyme is involved in transferring an acyl group from one diacylglycerol to another?

Diacylglycerol transacylase Signup and view all the answers

What is the outcome of the investigation regarding DGAT1 and chylomicron synthesis?

Chylomicron synthesis can occur without DGAT1. Signup and view all the answers

Which of the following statements about DAG transacylase activity is correct?

It remains similar in both WT and Dgat1-/- mice. Signup and view all the answers

What type of mice were utilized to study the function of DGAT1 in the intestine?

Dgat1-/- mice Signup and view all the answers

Which of the following is NOT a research question posed regarding DGAT1?

Can DGAT1 deﬁcient mice synthesize normal levels of cholesterol? Signup and view all the answers

What are the primary components formed when diacylglycerol transacylase acts on diacylglycerol?

Triacylglycerol and monoacylglycerol Signup and view all the answers

What is the primary significance of studying DGAT1 in the context of TAG absorption?

To understand its function in intestinal TAG synthesis Signup and view all the answers

How are newly synthesized triacylglycerols processed after assembly in the enterocyte?

They are packaged into chylomicrons in the Golgi apparatus. Signup and view all the answers

What is the role of DGAT1 in the metabolism of dietary fats when high fat intake occurs?

DGAT1 is not important for TAG metabolism Signup and view all the answers

What happens to dietary fat in the large intestine in the absence of DGAT1?

No dietary fat is found in the large intestine Signup and view all the answers

Which enzymes compensate for the loss of DGAT1 function in Dgat1-/- mice?

DAG transacylase and DGAT2 Signup and view all the answers

What is the evolutionary significance of TAG absorption mechanisms?

To maximize energy sources during food scarcity Signup and view all the answers

What is the potential therapeutic application of inhibiting DGAT-1?

Treatment for hypertriglyceridemia and insulin resistance Signup and view all the answers

Which of the following is true regarding DGAT-2 deficiency?

It is lethal Signup and view all the answers

What effect does high dietary fat have on chylomicronemia in the absence of DGAT1?

Decreased chylomicronemia Signup and view all the answers

Where is DGAT-2 primarily expressed in the body?

Liver, intestine, and white adipose tissue Signup and view all the answers

Study Notes

Triacylglycerol (TAG) Synthesis and Absorption

TAGs, also known as triglycerides, are composed of a glycerol backbone with three fatty acid tails.
Chylomicrons are lipoproteins responsible for transporting dietary fats. They are synthesized in the enterocytes of the small intestine.
Enzymes involved in TAG synthesis:
- Monoacylglycerol acyltransferase (MGAT)
- Diacylglycerol acyltransferase (DGAT) 1 and 2
- Diacylglycerol transacylase

DGAT1 Deficiency and Its Effects

Researchers used Dgat1-/- mice to investigate the role of DGAT1 in intestinal TAG metabolism and chylomicron synthesis.
Dgat1-/- mice exhibited reduced postabsorptive chylomicronemia when challenged with an acute lipid load.
Dgat1-/- mice displayed a buildup of neutral-lipid droplets in enterocytes when chronically fed a high-fat diet.
Dgat1-/- mice had reduced plasma levels of [125I]BMIPP, a marker for intestinal lipid absorption, and retinol.

Alternative Mechanisms for TAG Synthesis

DGAT2 and DAG transacylase compensate for the absence of DGAT1 in Dgat1-/- mice.
DGAT2 expression is highest in the proximal regions of the small intestine.
DGAT activity is markedly reduced in Dgat1-/- mice compared to wild-type mice.
DAG transacylase activity is similar in both wild-type and Dgat1-/- mice.

Conclusions and Future Directions

DGAT1 is not essential for intestinal TAG absorption, but it plays a significant role in chylomicron synthesis.
Redundant mechanisms for TAG processing exist, suggesting a crucial evolutionary requirement for efficient lipid absorption.
Future research should focus on the specific roles of DGAT2 and DAG transacylase in TAG synthesis and absorption.

Interesting Findings Since the Paper's Publication

DGAT1 is expressed ubiquitously, while DGAT2 is primarily found in the liver, intestine, and white adipose tissue.
DGAT-2 deficiency is lethal, while DGAT-1 deficiency results in resistance to diet-induced obesity, insulin resistance, and hepatic steatosis.
Inhibits DGAT1 might be a potential therapeutic strategy for hypertriglyceridemia and insulin resistance.

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Description

Explore the complex processes of triacylglycerol (TAG) synthesis and the implications of DGAT1 deficiency on lipid metabolism. Understand how chylomicrons transport dietary fats and the role of specific enzymes in TAG formation. This quiz delves into the physiological effects observed in Dgat1-/- mice and their relevance to dietary fat absorption.