The Translational Regulation of Lipoprotein Lipase in Diabetic Rats Involves the 3′-Untranslated Region of the Lipoprotein Lipase mRNA

Q: What does this research mean for the field?

The decrease in adipose tissue lipoprotein lipase (LPL) activity in insulin-deficient diabetes is predominantly caused by translation inhibition, which is mediated by the interaction of a cytoplasmic factor with specific sequences in the 3'-untranslated region (UTR) of the LPL mRNA. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Gouri Ranganathan; Chunling Li; Philip A. Kern

doi:10.1074/jbc.m008775200

December 1, 2000Journal of Biological ChemistryOpen Access

The Translational Regulation of Lipoprotein Lipase in Diabetic Rats Involves the 3′-Untranslated Region of the Lipoprotein Lipase mRNA

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Why the study?

Does insulin treatment reverse the decrease in adipose tissue LPL activity and synthetic rate in rats with streptozotocin-induced diabetes?

Key Points

To determine the molecular mechanism responsible for reduced adipose tissue lipoprotein lipase (LPL) activity in insulin-deficient diabetic rats.
Male Sprague-Dawley rats were divided into control, streptozotocin-induced diabetic (60 mg/kg), and insulin-treated diabetic groups (n=10–12 per group).
Assessed adipose LPL catalytic activity, measured LPL synthetic rates using [35S]methionine pulse labeling, quantified LPL mRNA levels by Northern blot, and analyzed polysome gradient profiles.
Characterized posttranscriptional mechanisms using in vitro reticulocyte lysate translation assays with truncated LPL transcripts and electrophoretic mobility gel shift assays.
Diabetic rats showed a 75–80% decrease in adipose heparin-releasable and extractable LPL activity (p < 0.01 vs. control) and a 75% reduction in LPL synthesis rate, both reversed by insulin therapy, despite unchanged total LPL mRNA levels.
Polysome profile distribution remained unchanged between control and diabetic adipocytes, indicating that diabetes does not impair translation initiation.
In vitro translation assays and gel shift analysis identified a trans-acting cytoplasmic factor in diabetic adipocytes that binds specifically to nucleotides 1818–2000 of the LPL 3′-untranslated region to repress translation.

Structured PICO

Does insulin treatment reverse the decrease in adipose tissue LPL activity and synthetic rate in rats with streptozotocin-induced diabetes?

P

Population

Male Harlan Sprague-Dawley rats (175–200 g) with streptozotocin-induced diabetes (n=10-12 per group)

I

Intervention

Insulin treatment (8 units of neutral protamine Hagedorn human insulin subcutaneously on each of the last 2 days before sacrifice)

C

Comparator

Control rats (injected with buffer) and untreated diabetic rats

O

Outcome

Adipose tissue LPL activity (heparin releasable and extractable) and LPL synthetic ratesurrogate

In an insulin-deficient rat model of diabetes, decreased adipose tissue LPL activity is primarily driven by translation inhibition involving the 3′-untranslated region of LPL mRNA, which is reversible with insulin treatment.

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Implication

Insulin reversal of adipose LPL loss in diabetic rats supports mechanistic studies on translational control; leaves open human applicability.

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Cite This Study

Ranganathan et al. (2000) studied this question.

synapsesocial.com/papers/6a1d2690ba65f5ee325de5e9 https://doi.org/10.1074/jbc.m008775200

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The Translational Regulation of Lipoprotein Lipase in Diabetic Rats Involves the 3′-Untranslated Region of the Lipoprotein Lipase mRNA

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

The Translational Regulation of Lipoprotein Lipase in Diabetic Rats Involves the 3′-Untranslated Region of the Lipoprotein Lipase mRNA

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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