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Cited by 80Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismNitric Oxide and Endothelin Effects

Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high fat-induced obese mice

Tsuchiya, Kyoichiro, Sakai, Haruna, Suzuki, Noriko, Iwashima, Fumiko, Yoshimoto, Takanobu, Shichiri, Masayoshi, Hirata, Yukio·2007·Endocrinology
DOI 10.1210/en.2006-1371
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Abstract

Genetic deletion of inducible nitric oxide synthase (NOS) in mice has been shown to improve high-fat diet (HFD)-induced insulin resistance. However, a pathophysiological role of endogenous nitric oxide (NO) in obesity-related insulin resistance remains controversial. To address this issue, we examined the metabolic phenotypes in HFD-induced obese mice with chronic blockade of NO synthesis by a NOS inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME). Six-week-old male C57BL/6j mice were provided free access to either a standard diet (SD) or a HFD and tap water with or without L-NAME (100 mg/kg.d) for 12 wk. L-NAME treatment significantly attenuated body weight gain of mice fed either SD or HFD without affecting calorie intake. L-NAME treatment in HFD-fed mice improved glucose tolerance and insulin sensitivity. HFD feeding induced inducible NOS mRNA expression, but not the other two NOS isoforms, in white adipose tissue (WAT) and skeletal muscle. L-NAME treatment up-regulated uncoupling protein-1 in brown adipose tissue of HFD-fed mice but down-regulated monocyte chemoattractant protein-1 and CD68 mRNAs levels in WAT. HFD feeding up-regulated leptin mRNA levels but conversely down-regulated adiponectin mRNA levels in WAT, but these effects were unaffected by L-NAME treatment. Moreover, L-NAME treatment also increased peroxisome proliferator-uncoupling protein-3 mRNA levels in skeletal muscles of HFD-fed mice. Increased urinary excretion of norepinephrine after HFD feeding was augmented in L-NAME-treated mice. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and serine phosphorylation of Akt/Akt2 in soleus muscle was markedly impaired in HFD-fed mice but reversed by L-NAME treatment. In conclusion, chronic NOS blockade by L-NAME in mice ameliorates HFD-induced adiposity and glucose intolerance, accompanied by reduced adipose inflammation and improved insulin signaling in skeletal muscle, suggesting that endogenous NO plays a modulatory role in the development of obesity-related insulin resistance.

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Crossref · 10.1210/en.2006-1371

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  • NOS inhibitors reduce adiposity and improve insulin sensitivity in high fat-fed mouse models.

    “as well as reduce adiposity and improve insulin sensitivity in high fat-fed mouse models [259]”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [259]

  • Chronic treatment with NOS inhibitors promotes weight loss and insulin sensitivity in animal models.

    “Although chronic treatment with NOS inhibitors promote weight loss and insulin sensitivity in animal models [253, 258, 259], acute applications of inhibitors of NOS cause systemic insulin resistance [287].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [259]

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Authors
Tsuchiya, K., Sakai, H., Suzuki, N., Iwashima, F., Yoshimoto, T., Shichiri, M., & Hirata, Y.
Affiliations
Tokyo Medical and Dental University (JP)
Corresponding author
Hirata, Yukio
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2007-10-01
Volume
148
Issue
10
Pages
4548-4556
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2006-1371
OpenAlex
W2093187404
Cited by
80
References
42
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 3
FWCI
4.13
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
nitric oxide, inducible nitric oxide synthase, L-NAME, high-fat diet-induced obesity, insulin resistance, impaired glucose tolerance, adipose tissue inflammation, brown adipose tissue, skeletal muscle insulin signaling, UCP1, MCP-1, leptin, adiponectin, norepinephrine, IRS-1
MeSH terms
Adipose Tissue, Animals, Blood Pressure, Catecholamines, Dietary Fats, Drug Administration Schedule, Enzyme Inhibitors, Glucose Tolerance Test, Inflammation, Insulin, Insulin Resistance, Isoenzymes, Male, Metabolism, Mice, Inbred C57BL, Nitrates, Nitrites, Obesity, Organ Size, Proteins, Signal Transduction, Gene Expression, Muscle, Skeletal, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Adiposity, Mice

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