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Dietary L-arginine supplementation increases the hepatic expression of AMP-activated protein kinase in rats

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Abstract

The goal of this study was to elucidate the molecular mechanisms responsible for the anti-obesity effect of L-arginine supplementation in diet-induced obese rats. Male Sprague–Dawley rats were fed either a low-fat or high-fat diet for 15 weeks. Thereafter, lean or obese rats were pair-fed their same respective diets and received drinking water containing either 1.51% L-arginine-HCl or 2.55% L-alanine (isonitrogenous control) for 12 weeks. Gene and protein expression of key enzymes in the metabolism of energy substrates were determined using real-time polymerase-chain reaction and western blotting techniques. The mRNA levels of hepatic fatty acid synthase and stearoyl-CoA desaturase were reduced (P < 0.05) but those of hepatic AMP-activated protein kinase-α (AMPKα), peroxisome proliferator activator receptor γ coactivator-1α, and carnitine palmitoyltransferase I (CPT-I), as well as skeletal muscle CPT-I were increased (P < 0.05) by L-arginine treatment. The protein expression and activity of hepatic AMPKα markedly increased (P < 0.05) but the activity of hepatic acetyl-CoA carboxylase (ACC) decreased (P < 0.05) in response to dietary L-arginine supplementation. Collectively, our results indicate that liver is the major target for the action of dietary L-arginine supplementation on reducing white-fat mass in diet-induced obese rats by inhibiting fatty acid synthesis and increasing fatty acid oxidation via the AMPK-ACC signaling pathway. Additionally, increased CPT-I expression in skeletal muscle may also contribute to the enhanced oxidation of long-chain fatty acids in L-arginine-supplemented rats.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

AMPK:

AMP-activated protein kinase

Arg:

L-Arginine

AU:

Arbitrary unit

BAT:

Brown adipose tissue

CPT-I:

Carnitine palmitoyltransferase I

DIO:

Diet-induced obesity

EDL:

Extensor digitorum longus

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GLUT:

Glucose transporter

MCD:

Malonyl-CoA decarboxylase

NOS:

Nitric oxide synthase

PGC-1α:

Peroxisome proliferator activator receptor γ coactivator-1 α

PKB:

Protein kinase B

RP:

Retroperitoneal

RT-PCR:

Real-time polymerase-chain reaction

SCD-1:

Stearoyl-CoA desaturase-1

SDS:

Sodium dodecyl sulfate

S6K1:

Ribosomal protein S6 kinase beta-1

TTBS:

Tris-Tween buffered saline

UCP:

Uncoupling protein

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Acknowledgements

We thank Dr. Stephen B. Smith and Dr. Cynthia J. Meininger for helpful discussion, as well as Mr. Scott Jobgen for laboratory analyses of metabolites. This work was supported by grants from American Heart Association–Texas (#0755024Y and #10GRNT4480020).

Funding

American Heart Association-Texas, #0755024Y, Guoyao Wu, #10GRNT4480020, Guoyao Wu.

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  1. Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX, 77843, USA

    Wenjuan S. Jobgen & Guoyao Wu

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  1. Wenjuan S. Jobgen
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Correspondence to Guoyao Wu.

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Jobgen, W.S., Wu, G. Dietary L-arginine supplementation increases the hepatic expression of AMP-activated protein kinase in rats. Amino Acids 54, 1569–1584 (2022). https://doi.org/10.1007/s00726-022-03194-w

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