Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats

Laughlin, M. Harold; Padilla, Jaume; Jenkins, Nathan T.; Thorne, Pamela K.; Martin, Jeffrey S.; Rector, R. Scott; Akter, Sharmin; Davis, J. Wade

doi:10.1152/japplphysiol.00316.2015

Cited by 20 publications

(49 citation statements)

References 69 publications

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“…A recent series of studies evaluated the effects of regular exercise on the vascular transcriptome in pigs (238) and rats (174,175,235). A common finding is that the effects of exercise are heterogeneous across vascular beds.…”

Section: Changes In Vascular Cell Gene Expression Induced By Exercmentioning

confidence: 99%

“…A common finding is that the effects of exercise are heterogeneous across vascular beds. In a recent and comprehensive study (174), next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology was used to assess the effects of exercise training on transcriptional profiles in skeletal muscle arterioles In addition, using RNA-sequencing, the extent to which the effects of obesity (i.e. differences between obese OLETF rats and lean-counterparts rats) on aortic endothelial gene expression could be reversed by endurance exercise was recently reported (146, 235).…”

Section: Changes In Vascular Cell Gene Expression Induced By Exercmentioning

confidence: 99%

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Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Green

Hopman

Padilla

et al. 2017

Physiological Reviews

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On the 400 th anniversary of Harvey's Lumleian lectures, this review focusses on the impact of physical exercise on "hemodynamic" forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20 th century discovery that endothelial cells modify arterial tone via paracrine transduction, provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the inter-relationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions and the implications for human health.Exercise modifies blood flow, luminal shear stress, arterial pressure and tangential wall stress, all of which can transduce changes in arterial function, diameter and wall thickness.There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute substantially to the well-established decrease in cardiovascular risk attributed to physical activity.

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Section: Changes In Vascular Cell Gene Expression Induced By Exercmentioning

confidence: 99%

Section: Changes In Vascular Cell Gene Expression Induced By Exercmentioning

confidence: 99%

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Green

Hopman

Padilla

et al. 2017

Physiological Reviews

Self Cite

530

570

View full text Add to dashboard Cite

show abstract

“…[15][16][17]27 Nevertheless, the notion that the effects of exercise are not the same among skeletal muscle arteries can be reconciled with the understanding that during exercise different muscle fiber recruitment patterns exist among these skeletal muscles, thus likely contributing to this differing vascular effect of training between muscles and even within muscles. 17,27 Perhaps more surprising was our recent finding that obesity, viewed as a condition with systemic complications, also resulted in striking heterogeneous effects among arteries examined. 24,28,29 Indeed, we identified 20 genes whose expression was consistently altered among 15 arteries, which represented only a $9% overlapping effect of obesity among all arteries examined.…”

Section: Discussionmentioning

confidence: 99%

“…The reader is referred to our recent publications for a visual of the anatomic location and structure of gastrocnemius and soleus vascular network. 17,23 RNA extraction, RNA quality control, library preparation, and RNA-seq were performed as described previously. 16,24 …”

Section: Isolation Of Arteries and Rna Sequencingmentioning

confidence: 99%

“…13 As in previous studies from our group, lack of changes in vasomotor function in response to an intervention does not imply an absence of a vascular phenotypic effect at the molecular level. [15][16][17] As such, to gain further insights into the impact of metformin on the vasculature, we assessed transcriptional profiles in skeletal muscle resistant arteries from the OLETF rats utilized in our previous study. 13 Specifically, we performed a transcriptome-wide RNA sequencing (RNASeq) analysis in the feed arteries and second branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles in metformin-treated (via drinking water for 12 weeks) versus untreated OLETF rats.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats

Padilla

Thorne

Martin

et al. 2017

Exp Biol Med (Maywood)

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This study provides evidence that metformin treatment produces artery-specific gene expression effects. The genes whose expression was modulated with metformin do not appear to have a clear connection with its known mechanisms of action. AbstractWe examined the effects of metformin, a commonly used antidiabetic drug, on gene expression in multiple arteries. Specifically, transcriptional profiles of feed arteries and second branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles as well as aortic endothelial scrapes were examined from obese insulin-resistant Otsuka Long-Evans Tokushima Fatty rats treated with (n ¼ 9) or without (n ¼ 10) metformin from 20 to 32 weeks of age. Metformin-treated rats exhibited a reduction in body weight, adiposity, and HbA1c (P < 0.05). The greatest number of differentially expressed genes (FDR < 15%) between those treated with and without metformin was found in the red gastrocnemius 2a arterioles (93 genes), followed by the diaphragm 2a arterioles (62 genes), and soleus 2a arterioles (15 genes). We also found that two genes were differentially expressed in aortic endothelial cells (LETMD1 and HMGCS2, both downregulated), one gene in the gastrocnemius feed artery (BLNK, downregulated), and no genes in the soleus and diaphragm feed arteries and white gastrocnemius 2a arterioles. No single gene was altered by metformin across all vessels examined. This study provides evidence that metformin treatment produces distinct gene expression effects throughout the arterial tree in a rat model of obesity and insulin resistance. Genes whose expression was modulated with metformin do not appear to have a clear connection with its known mechanisms of action. These findings support the notion that vascular gene regulation in response to oral pharmacological therapy, such as metformin, is vessel specific.

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Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD

et al. 2022

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Background and Aims NAFLD and its more‐advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver‐related, and all‐cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant. Approach and Results To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline‐NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite‐NASH (D‐NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate‐limiting enzyme in β‐oxidation (β‐hydroxyacyl‐CoA dehydrogenase activity) were reduced by ~40%–50% with D‐NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH. Conclusions These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.

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Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats

Cited by 20 publications

References 69 publications

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats

Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD

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