Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates

Jobgen, Wenjuan S.; Fried, Susan K.; Fu, Wenjiang; Meininger, Cynthia J.; Wu, Guoyao

doi:10.1016/j.jnutbio.2005.12.001

Cited by 619 publications

(523 citation statements)

References 149 publications

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“…Conversely, inhibition of NO formation by the NOS inhibitor L-NAME diminishes AMPK activation by the antidiabetic drug metformin. Importantly, in eNOS Ϫ/Ϫ mice, metformin (16) or shear stress (17) had no effect on AMPK activity in endothelial cells, emphasizing the importance of endogenous NO in AMPK activation and subsequent metabolism of energy substrates.…”

mentioning

confidence: 99%

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Zhang

Xie

Dong

et al. 2008

Journal of Biological Chemistry

105

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2؉ chelator, indicating that NO-induced AMPK activation is guanylyl cyclase-mediated and calcium-dependent. Exposure of HUVECs or isolated mice aortas to either calcium ionophore A23187 or bradykinin significantly increased AMPK Thr-172 phosphorylation, which was abolished by N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Finally, A23187-or bradykinin-enhanced AMPK activation was significantly greater in aortas from wild type mice than those in the aortas of endothelial nitric oxide synthase knock-out mice. Taken together, we conclude that NO might act as an endogenous AMPK activator.The AMP-activated protein kinase (AMPK) 2 is a key enzyme in an important energy-sensing/signaling system by which cells sense and decode changes in energy status. The overall effect of AMPK activation is to switch off ATP-consuming pathways such as lipogenesis or gluconeogenesis, whereas switching on ATP-producing pathways such as fatty acid and glucose oxidation. AMPK is a protein consisting of three subunits designated ␣, ␤, and ␥. The ␣ subunit is the catalytic subunit containing the kinase domain, which transfers a phosphate from ATP to the target protein. The ␤ and ␥ subunits are considered regulatory components (1-3). All three subunits are required for expression of full activity (4).Phosphorylation of Thr-172 on the ␣ subunit by upstream kinases, AMPK kinases, results in AMPK activation. Several upstream kinases have been identified, including a complex of the tumor suppressor protein LKB1 and two accessory subunits, termed STRAD and MO25 (5, 6), and Ca 2ϩ /calmodulindependent protein kinase kinase (CaMKK), especially the CaMKK ␤ isoform (7-9). AMP also allosterically promotes phosphorylation at Thr-172 by LKB1 (10, 11). Any situation that causes an increase in cytoplasmic Ca 2ϩ will create a subsequent demand for ATP because Ca 2ϩ is immediately pumped out of the cytoplasm using ATP-driven pumps in the plasma membrane and endoplasmic reticulum. Activation of AMPK under these circumstances may represent a mechanism to anticipate the demand for ATP created by Ca 2ϩ entry. Nitric oxide (NO) is a small, highly reactive, diffusible free radical that has been implicated in many physiological and pathophysiological processes. NO exerts its effects through many ways including activation of the cGMP/protein kinase G pathway and through S-nitrosylation of proteins (12). There is an emerging body of evidence indicating a relationship between NO and AMPK expression/activity in cells (13). Such a relationship cooperatively promotes glucose and fatty acid oxidation. There is ample evidence showing that AMPK regulates NO production in cells. For example, endothelial nitric oxide synthase (eNOS) is phosphorylated by AMPK at position Ser-*

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mentioning

confidence: 99%

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Zhang

Xie

Dong

et al. 2008

Journal of Biological Chemistry

105

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“…1 Among these are potential decreases in mitochondrial biogenesis and oxidative phosphorylation; activation of specific transcription factors and signaling pathways and reductions in blood flow to areas of high metabolic demand such as skeletal muscle. It is plausible therefore that improvements in muscle blood flow, and insulin sensitivity, which occur secondarily to improvements in endothelial function may be useful for the prevention or management of obesity.…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence that, in addition to the well-documented adverse cardiovascular effects, reduced availability of NO can impair metabolic function. 1 Among the proposed mechanisms for this is a reduction in blood flow to areas of high metabolic demand such as skeletal muscle. 1 Flow-mediated dilatation (FMD) of the brachial artery is used to assess the NO-dependent endothelium-mediated dilatory response of an artery and, as such, provides a marker of endothelial function.…”

Section: Introductionmentioning

confidence: 99%

“…1 Among the proposed mechanisms for this is a reduction in blood flow to areas of high metabolic demand such as skeletal muscle. 1 Flow-mediated dilatation (FMD) of the brachial artery is used to assess the NO-dependent endothelium-mediated dilatory response of an artery and, as such, provides a marker of endothelial function. In recent years, the consumption of cocoa products containing flavanols and procyanidins (oligomeric flavanols) has been shown to elicit dosedependent acute improvements in FMD, and regular consumption for up to 14 days provides a sustained improvement in FMD.…”

Section: Introductionmentioning

confidence: 99%

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Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects

et al. 2008

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Objective: Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. Design: Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 Â 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). Results: A total of 49 subjects (M ¼ 18; F ¼ 31) completed the intervention. Baseline averages were as follows: body mass index ¼ 33.5 kg/m 2 ; BP ¼ 123/76 mm Hg; HOMA2 ¼ 2.4; FMD ¼ 4.3%; rate of fat oxidation during exercise ¼ 0.34 g min À1 ; abdominal fat ¼ 45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (Po0.01) and chronically (over 12 weeks; Po0.01) by 1.6% and reduced insulin resistance by 0.31% (Po0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (Po0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min À1 (Po0.01) and reduced abdominal fat by 0.92% (Po0.05). Conclusion: Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

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“…In the pig, undernutrition in utero causes low birth weight, and decrease in muscle fibre number and a reduction in postnatal growth rate, but the growth rate could be improved with increasing the feeding level (Campbell et al 1984;Dwyer et al 1994). Intestine, liver, kidney and pancreas are important organs involved in digestion, absorption and metabolism of dietary nutrients (Jobgen et al 2006;Han et al 2013) IUGR was found to reduce the visceral organ weight, impair intestinal growth by decreasing cell number and size as well as reduce the villi height. Our findings showed that IUGR piglets exhibited differential adipose deposition and mRNA expressions of lipid metabolism related to liver, abdominal fat and muscle by HN.…”

Section: Discussionmentioning

confidence: 99%

The effect of high nutrient on the growth performance, adipose deposition and gene expression of lipid metabolism in the neonatal intrauterine growth-retarded piglets

Chen

Mao

Han

et al. 2015

Journal of Applied Animal Research

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Twelve pairs of intrauterine growth retardation (IUGR,1.84 ± 0.09 kg) and normal birth weight (NBW, 2.80 ± 0.16 kg) of Duroc × Landrace × Yorkshire piglets (7-day old) were randomly assigned to four treatments (six replicates per treatment) in a 2 × 2 factorial design. IUGR and NBW piglets were fed diets of either normal nutritional level (NN, 880 kcal/L, 50 g of protein/L) or high nutritional level (HN, 1320 kcal/L, 75 g protein/L)for 21 days. IUGR decreased the average daily dry matter intake (ADMI), the average daily growth (ADG) and leaf fat relative weight. Regardless of body weight, HN could increase the ADMI, ADG and intramuscular fat content, and enhance serum insulin, IGF-I and leptin concentrations, but decreased serum adiponectin concentrations in IUGR piglets. Furthermore, HN could increase the PGC-1α of liver and C/EBPα of longissimus expression in IUGR piglets. These results suggested that the IUGR piglets had lower growth performance and adipose deposition than NBW piglets. However, HN in diets could make up the defect of IUGR piglets in the uterus, and regulated the expression of lipid metabolism genes in some tissues of IUGR piglets. ARTICLE HISTORY

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Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates

Cited by 619 publications

References 149 publications

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects

The effect of high nutrient on the growth performance, adipose deposition and gene expression of lipid metabolism in the neonatal intrauterine growth-retarded piglets

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