Effect of Behavioral Interventions on Insulin Sensitivity and Atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbit

Gonzales, Julie A.; Szeto, Angela; Mendez, Armando J.; Zaias, Julia; Paredes, Jamespaul; Caperton, Caroline V.; Llabre, María M.; Levine, Jon E.; Goldberg, Ronald; Schneiderman, Neil; McCabe, Philip M.

doi:10.1097/01.psy.0000155674.95497.ab

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…Interventions designed to increase physical activity through forced exercise on a treadmill have failed to affect the progression of atherosclerosis in individually-caged WHHL rabbits (20), however, studies utilizing voluntary exercise in other models of hypercholesterolemia have proved more effective (18). Future research examining the effects of voluntary exercise in WHHL may further support the finding that sedentary behavioral context leads to increased NAD(P)H-oxidase activity.…”

Section: Discussionmentioning

confidence: 96%

The Effect of Social Environment on Markers of Vascular Oxidative Stress and Inflammation in the Watanabe Heritable Hyperlipidemic Rabbit

Nation

Gonzales

Mendez

et al. 2008

Psychosomatic Medicine

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The results suggest that social environment creates distinct behavioral contexts that can affect markers of inflammation and oxidative stress early in the development of atherosclerosis. Specifically, physical inactivity associated with individual caging affects indices of oxidative stress and inflammation. These pathophysiological markers may help to explain behaviorally related differences in the extent of atherosclerosis observed in prior studies.

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Section: Discussionmentioning

confidence: 96%

The Effect of Social Environment on Markers of Vascular Oxidative Stress and Inflammation in the Watanabe Heritable Hyperlipidemic Rabbit

Nation

Gonzales

Mendez

et al. 2008

Psychosomatic Medicine

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“…Because they did not have a conspecific with whom to interact, the Individually Caged Group spent a greater percentage of their time behaviorally inactive relative to the other groups. We have hypothesized that this type of sedentary behavior, coupled with increased visceral fat and body weight due to overeating and hyperinsulinemia, could lead to the development of the “metabolic syndrome” and chronic sympathetic nervous system arousal (McCabe et al, 2002; Gonzales et al, 2005). …”

Section: Discussionmentioning

confidence: 99%

The influence of social environment on endocrine, cardiovascular and tissue responses in the rabbit

Noller

Szeto

Mendez

et al. 2013

International Journal of Psychophysiology

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Previous work from our lab demonstrated that social environment influences the progression of atherosclerosis in genetically hyperlipidemic rabbits. The purpose of the current study was to examine behavioral and physiological responses associated with these distinct chronic social conditions. Normolipidemic rabbits were exposed to one of 3 social environments for 4 hours/day over 20 weeks: 1) an Unstable Group in which animals were paired weekly with a different unfamiliar rabbit, 2) a Stable Group in which rabbits were paired with the same littermate for the entire study, and 3) an Individually Caged Group in which animals were socially isolated. It was found that the Unstable Group, characterized by increased agonistic behavior and relatively less affiliative behavior, exhibited physiological responses indicative of chronic stress (increased urinary norepinephrine, plasma cortisol, splenic weight, and decreased visceral fat and body weight compared to the other groups). These animals also had increased acute plasma oxytocin responses relative to the other groups 10 minutes into the social pairing. In contrast, the Stable Group exhibited more affiliative behavior and less stressful physiological and tissue responses. The Individually Caged Group had elevated urinary norepinephrine relative to the Stable Group, and they exhibited higher heart rates at the end of the study compared to the other groups, suggesting that this social environment is also associated with chronic sympathetic arousal. It was concluded that distinct social contexts lead to different patterns of behavioral and physiological responses, and these responses are relevant to the pathophysiology of atherosclerosis and cardiovascular disease.

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“…We include data from cells at subconfluence and withdraw serum at 90-100% confluence whilst Deldicque et al [29] withdrew serum at 70% confluence. Gonzalez et al [31] include data from cells at subconfluence however they collected their cells at a higher confluence and they plated their cells on gelatin coated plates which could affect the cell surface receptors that may be involved in PKB activation. These differences may explain why Gonzalez et al did not observe an initial reduction in PKB Thr308 phosphorylation upon reaching confluence.…”

Section: Discussionmentioning

confidence: 99%

Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation

et al. 2010

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BackgroundMyogenesis in C2C12 cells requires the activation of the PI3K/mTOR signaling pathways. Since mTOR signaling can feedback through S6K1 to inhibit the activation of PI3K, the aim of this work was to assess whether feedback from S6K1 played a role in myogenesis and determine whether siRNA mediated knockdown of S6K1 would lead to an increased rate of myotube formation.ResultsS6K1 activity increased in a linear fashion following plating and was more than 3-fold higher after Day 3 of differentiation (subconfluent = 11.09 ± 3.05, Day 3 = 29.34 ± 3.58). IRS-1 levels tended to increase upon serum withdrawal but decreased approximately 2-fold (subconfluent = 0.88 ± 0.10, Day 3 = 0.42 ± 0.06) 3 days following differentiation whereas IRS-2 protein remained stable. IRS-1 associated p85 was significantly reduced upon serum withdrawal (subconfluent = 0.86 ± 0.07, Day 0 = 0.31 ± 0.05), remaining low through day 1. IRS-2 associated p85 decreased following serum withdrawal (subconfluent = 0.96 ± 0.05, Day 1 = 0.56 ± 0.08) and remained suppressed up to Day 3 following differentiation (0.56 ± 0.05). Phospho-tyrosine associated p85 increased significantly from subconfluent to Day 0 and remained elevated throughout differentiation. siRNA directed against S6K1 and S6K2 did not result in changes in IRS-1 levels after either 48 or 96 hrs. Furthermore, neither 48 nor 96 hrs of S6K1 knockdown caused a change in myotube formation.ConclusionsEven though S6K1 activity increases throughout muscle cell differentiation and IRS-1 levels decrease over this period, siRNA suggests that S6K1 is not mediating the decrease in IRS-1. The decrease in IRS-1/2 associated p85 together with the increase in phospho-tyrosine associated p85 suggests that PI3K associates primarily with scaffolds other than IRS-1/2 during muscle cell differentiation.

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Effect of Behavioral Interventions on Insulin Sensitivity and Atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbit

Cited by 6 publications

References 27 publications

The Effect of Social Environment on Markers of Vascular Oxidative Stress and Inflammation in the Watanabe Heritable Hyperlipidemic Rabbit

The Effect of Social Environment on Markers of Vascular Oxidative Stress and Inflammation in the Watanabe Heritable Hyperlipidemic Rabbit

The influence of social environment on endocrine, cardiovascular and tissue responses in the rabbit

Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation

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