cardiovascular system
• small increase in cardiac glycogen content at 12 months of age
• however, cardiac histology and ultrastructure appear normal
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• sinoatrial node shows excess of glycogen
• increase in maximal sinoatrial node thickness
• however, no evidence of apoptosis is seen
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• mice exhibit a subtle reduction in cardiac contractile performance at 2 months of age, with no progression at 10 months of age
• however, no left ventricular hypertrophy or left ventricle dilatation is seen
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• isolated perfused hearts show a lower intrinsic heart rate
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• mice under isoflurane general anesthesia show a reduction in sinus heart rate
• however, PR interval and anterograde atrioventricular conduction parameters are normal
• isolated sinoatrial cells exhibit reduced basal firing rate but unaltered maximum diastolic potential
• however, sinoatrial cells retain high responsivity to catecholamine and cholinergic rate modulation
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• sinoatrial cells show a reduction in sarcolemmal hyperpolarization-activated funny current, I(f), density with a reduction in whole-cell I(f) conductance compared to wild-type
• however, no alteration in the I(f) voltage-dependence of activation
• sinoatrial cells exhibit a lower mean spontaneous rhythmic sarcoplasmic reticulum local calcium release (LCR) amplitude, size, and duration, resulting in more than 50% lower spontaneous calcium signal of individual and ensemble LCRs
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adipose tissue
• at 40 weeks of age
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• at 40 weeks of age
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• at 40 weeks of age
• increases in plasma proinflammatory cytokines and up-regulation of white adipose tissue expression of Tnf and Adgre1
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muscle
• small increase in cardiac glycogen content at 12 months of age
• however, cardiac histology and ultrastructure appear normal
|
• sinoatrial node shows excess of glycogen
• increase in maximal sinoatrial node thickness
• however, no evidence of apoptosis is seen
|
• mice exhibit a subtle reduction in cardiac contractile performance at 2 months of age, with no progression at 10 months of age
• however, no left ventricular hypertrophy or left ventricle dilatation is seen
|
behavior/neurological
polyphagia
(
J:235379
)
• increased excitability of arcuate nucleus Agrp-expressing neurons and elevations of their cognate neuropeptides
• exaggerated feeding and weight gain responses after fasting: enhanced fasting-induced neuronal activation
• pair-feeding experiments matching daily food intake to that of wild-type normalized body weight
• 2.5-fold greater Bsx expression in freely fed mice, raising Agrp and Npy expression in arcuate nucleus neurons which alters post-fast and ghrelin-induced feeding
• sensitivity to exogenous ghrelin: greater acute feeding response
• enhanced gain on ghrelin-responsive orexigenic circuitry lowers threshold for feeding
• Ghsr inhibition normalizes hyperphagia
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endocrine/exocrine glands
• significant enrichment for upregulated genes with potential to alter glucose metabolism and insulin secretion, and genes relevant to oxidative stress, cell proliferation, and exocytosis
• Ghsr antagonist normalized the insulin secretory response 30 minutes post-glucose without affecting glucose tolerance or basal insulin levels
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growth/size/body
• at 40 weeks of age
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• hypoadiponectinemia with reduced white adipose tissue expression and hyperleptinemia
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homeostasis/metabolism
• small increase in cardiac glycogen content at 12 months of age
• however, cardiac histology and ultrastructure appear normal
|
• basal and glucose-stimulated levels in young pre-obese mice
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immune system
• at 40 weeks of age
• systemic inflammation
• increases in plasma proinflammatory cytokines and up-regulation of white adipose tissue expression of Tnf and Adgre1
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• at 40 weeks of age
• increases in plasma proinflammatory cytokines and up-regulation of white adipose tissue expression of Tnf and Adgre1
|
liver/biliary system
• at 40 weeks of age
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