Circadian Neuroendocrine Role in Age-Related Changes in Body Fat Stores and Insulin Sensitivity of the Male Sprague-Dawley Rat

Cincotta, Anthony H.; Schiller, B; Landry, Roger J.; Herbert, Stephen J.; Miers, Wendell R.; Meier, Albert

doi:10.1080/07420529309059707

Cited by 35 publications

(23 citation statements)

References 46 publications

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“…Moreover, the concentration of CGRP in blood of old rats, about 70 pM (37,38), might even be capable of antagonizing the action of insulin, since a maximum inhibition of insulin-stimulated glucose uptake by soleus muscle in vitro is achieved at a peptide concentration of 10 pM (23). A rise in insulin resistance has been reported in old rats, starting between 2 and 4 months of age and reaching a maximum at 12 months (3,13,29,31). Moreover, an increase in CGRP concentration in blood has been demonstrated in obese fdfa rats (36) and in obese humans (41).…”

Section: Discussionmentioning

confidence: 99%

Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

Melnyk

Himms‐Hagen

1995

Obesity Research

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Resistance to aging-associated obesity in capsaicindesensitized rats one year after treatment. Obes Res.Previous studies demonstrated reduced weight of abdominal white adipose tissue depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months after treatment. The objective of the present study was to find out whether aging-associated obesity and hyperplasia of retroperitoneal white adipose tissue was prevented in older (13.5 month old) CapDes rats, one year after treatment with Cap (done when they were 1.5 months old). The prevalence of obesity is known to increase in rats by this age. Abdominal white adipose tissue depots weighed less in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less). The number of mature white adipocytes was 28% less in the retroperitoneal depot but was not significantly different in the epididymal depot. Adipocyte size was not different. Carcass fat was less, both total and as percent of body weight. Food intake was normal for their reduced body size. The exponential increase in retroperitoneal white adipose tissue weight characteristic of aging rats that are becoming obese was virtually absent in Cap-Des rats. We conclude that lack of function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed in Cap-Des rats, results in an alteration in energy balance conducive to leanness. We suggest that the attenuated MELNYK, ANNA AND JEAN HIMMS-HAGEN. age-associated increase in circulating CGRP (derived mainly from capsaicin-sensitive nerves) in the CapDes rat results in a lower degree of aging-associated insulin-resistance, hence in a lesser degree of obesity.

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Section: Discussionmentioning

confidence: 99%

Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

Melnyk

Himms‐Hagen

1995

Obesity Research

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“…The nocturnal rise in circulating leptin levels of younger animals is attenuated in older animals, including primates (Downs and Urbanski, 2006). The phases and amplitudes of rhythms of hormones associated with metabolic function, such as insulin, corticosterone, and prolactin, are disrupted in obese aged rodents and administration of these hormones at specific times of day mimicking the rhythms of the younger phenotype are able to re-establish metabolic characteristics of younger animals (Cincotta et al, 1993). Age-related alterations in corticosterone secretion are a direct result of the eradication of the diurnal rhythm of its hypothalamic releasing peptide, corticotropin-releasing hormone (CRH) (Cai and Wise, 1996).…”

Section: Aging and Circadian Changes In Energeticsmentioning

confidence: 98%

Aging in the circadian system: Considerations for health, disease prevention and longevity

Gibson

Williams

Kriegsfeld

2009

Experimental Gerontology

138

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The circadian system orchestrates internal physiology on a daily schedule to promote optimal health and maximize disease prevention. Chronic disruptions in circadian function are associated with an increase in a variety of disease states including, heart disease, ulcers, and diabetes. With advanced age, the genes regulating circadian function at the cellar level become disorganized and the ability of the brain clock to entrain to local time diminishes. As a result, aged individuals exhibit a loss of temporal coordination among bodily systems, leading to deficits in homeostasis and sub-optimal functioning. Such disruptions in the circadian system appear to accelerate the aging process and contribute to senescence, with some systems being more vulnerable than others. This review explores aging-associated changes in circadian function and examines evidence linking such alterations to adverse health consequences in late life and promotion of the aging process.

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“…Specifically, temporal changes in the interaction of 2 distinct neural circadian oscillations, mediated by dopaminergic and serotonergic neurotransmitter activity, have been shown to regulate the dramatic seasonal alterations in body weight and body composition that are characteristic of all vertebrate classes from teleosts to mammals (7). Data obtained in rats, pigs, and humans suggest that similar mechanisms may play a role in the development of nonseasonal obesity and insulin resistance (7)(8)(9).…”

Section: Diabetes Care 23:1154-1161 2000mentioning

confidence: 99%

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

et al. 2000

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. R.A.D. has served on the advisory board and as a paid consultant for Ergo Science. A.H.C. is a member of the Board of Directors of Ergo Science and holds stock in that company.Abbreviations: CV, coefficient of variation; EGP, endogenous glucose production; FFA, free fatty acid; FFM, fat-free mass; FPG, fasting plasma glucose; GIR, exogenous glucose infusion rate; MRI, magnetic resonance imaging; OGTT, oral glucose tolerance test; R a , rate of endogenous glucose appearance.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. BromocriptineA novel approach to the treatment of type 2 diabetesOBJECTIVE -In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects.RESEARCH DESIGN AND METHODS -There were 22 obese subjects with type 2 diabetes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentration and HbA 1c were measured at 2-to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU и min Ϫ1 и m Ϫ2 ) were measured before and after treatment.RESULTS -No changes in body weight or body composition occurred during the study in either placebo-or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA 1c (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA 1c (⌬ = 1.2%, P = 0.01) and fasting glucose (⌬ = 54 mg/dl, P Ͻ 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant. The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine-or placebo-treated group. During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg и min Ϫ1 и kg Ϫ1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg и min Ϫ1 и kg Ϫ1 FFM (P Ͻ 0.05), whereas ...

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Circadian Neuroendocrine Role in Age-Related Changes in Body Fat Stores and Insulin Sensitivity of the Male Sprague-Dawley Rat

Cited by 35 publications

References 46 publications

Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

Resistance to Aging‐Associated Obesity in Capsaicin‐Desensitized Rats One Year after Treatment

Aging in the circadian system: Considerations for health, disease prevention and longevity

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

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