Adrenal Involvement in Scrapie-Induced Obesity

Kim, Yong S.; Carp, Richard I.; Callahan, Sharon M.; Wı́sniewski, Henryk M.

doi:10.3181/00379727-189-42774

Cited by 37 publications

(26 citation statements)

References 7 publications

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“…These fluctuations did not exist for cortisol plasma or urine metabolites due to the dampening effect of the metabolic process on the short-term variations of cortisol secretion (Schelcher et al 1999). When the plasma cortisol metabolites (20 -dihydrocortisol, cortisone) are taken into account, the results of the present experiment are consistent with the observed stimulation of the adrenal function in scrapie-affected ewes demonstrated in a previous study (Schelcher et al 1999) and the enlargement of the adrenal cortex observed in scrapieaffected ewes (Beck et al 1964), in experimentally infected mice (Kim et al 1988) and in hamsters infected with the 139H scrapie strain (Carp et al 1990).…”

Section: Discussionsupporting

confidence: 80%

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Picard‐Hagen

Gayrard²,

Alvinerie³

et al. 2000

Journal of Endocrinology

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Naturally scrapie-affected ewes present a syndrome of hypercortisolism as evaluated by measuring total plasma cortisol concentrations. The objective of this study was to investigate the plasma protein binding of cortisol and to evaluate the concentration of the biologically active free fraction of cortisol in scrapie-affected ewes. Corticosteroid binding globulin (CBG) binding parameters were evaluated by equilibrium dialysis in 13 naturally scrapie-affected ewes and nine healthy ewes, during two periods of the clinical evolution of the disease. The hypercortisolism of the scrapie-affected ewes was confirmed by a significant increase of the plasma 20 -dihydrocortisol and cortisone concentrations, while total cortisol concentrations, obtained from an isolated sample, did not differ between scrapie-affected and control ewes. The scrapie diagnosis was confirmed by histopathology. The CBG maximal capacity (B max ) was two times lower in scrapieaffected ewes than in healthy ewes (37 32 nM and 73 28 nM respectively). The dissociation constant K d (8·8 3·7 nM and 9·8 3·0 nM respectively) and the non-specific constant value of binding to albumin (1·13 0·18 and 1·14 0·23 respectively) did not differ significantly between diseased and control ewes. The significant increased concentrations of CBG-free cortisol (i.e. both albumin-bound and free cortisol fractions) in scrapie-affected ewes indicates that total plasma cortisol concentration is not an appropriate index of pituitary-adrenocortical hyperactivity.In conclusion, ewes with naturally occurring scrapie display a syndrome of hypercortisolism associated with a lower CBG binding capacity which leads to an overexposure of glucocorticoid-sensitive targets to CBG-free cortisol. The physiopathological consequences of this overexposure on the development of the neurodegenerative process in prion disease are discussed.

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Section: Discussionsupporting

confidence: 80%

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Picard‐Hagen

Gayrard²,

Alvinerie³

et al. 2000

Journal of Endocrinology

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“…Endocrine alterations in hamsters infected with the 139H strain of the scrapie agent (hereafter, 139H scrapie) have also been reported (Carp et al 1989, Ye et al 1994a,b, 1997, Ye & Carp 1995; for reviews, see Carp et al 1990Carp et al , 1994 including obesity, pronounced hyperinsulinemia, altered glucose tolerance and/or insulin resistance (Carp et al 1989, Srinivasappa et al 1989. In mouse models of prion disease, endocrine alterations range from hyperinsulinemia and adrenaldependent obesity to loss of body weight and reduced adiposity (Carp et al 1984, Kim et al 1987, 1988. In fact, the loss of body weight and adiposity is common in several naturally occurring prion diseases, including sheep and goats with scrapie (Capucchio et al 2001), in wild ungulates with chronic wasting disease (Miller & Williams 2002; for review see Salman 2003), and in humans with either fatal familial insomnia or CreutzfeldtJakob disease (Collinge 2001).…”

Section: Introductionmentioning

confidence: 99%

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

Bailey

Berardinelli

Rocke

et al. 2008

Journal of Endocrinology

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Prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. The basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139H strain of scrapie agent, which induces preclinical weight gain, or the HY strain of transmissible mink encephalopathy (TME), which induces clinical weight loss. Temporal changes in body weight, feed, and water intake were measured as well as both non-fasted and fasted concentrations of serum glucose, insulin, glucagon, b-ketones, and leptin. In 139H scrapie-infected hamsters, polydipsia, hyperphagia, non-fasted hyperinsulinemia with hyperglycemia, and fasted hyperleptinemia were found at preclinical stages and are consistent with an anabolic syndrome that has similarities to type II diabetes mellitus and/or metabolic syndrome X. In HY TME-infected hamsters, hypodipsia, hypersecretion of glucagon (in both non-fasted and fasted states), increased fasted b-ketones, fasted hypoglycemia, and suppressed non-fasted leptin concentrations were found while feed intake was normal. These findings suggest a severe catabolic syndrome in HY TME infection mediated by chronic increases in glucagon secretion. In both models, alterations of pancreatic endocrine function were not associated with PrP Sc deposition in the pancreas. The results indicate that prominent endocrinopathy underlies alterations in body weight, pancreatic endocrine function, and intake of food. The prion-induced alterations of energy homeostasis in 139H scrapie-or HY TME-infected hamsters could occur within areas of the hypothalamus that control food satiety and/or within autonomic centers that provide neural outflow to the pancreas.

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“…with ME7 and in C57BL mice injected in the hypothalamus with ME7 (Kim et al, 1988). In the present study, adrenalectomy prevented the weight increase induced by line C602 (Fig.…”

Section: The Effect Of Adrenalectomy On the Induction Of Obesity And mentioning

confidence: 56%

“…Changes were also seen in open-field and Y-maze exploration scores (McFarland et al, 1980) and in apomorphine-induced circling behaviour after unilateral stereotaxic injection of the nigrostriatal system (Gorde et al, 1982). Our recent studies which focused on the obesity seen before motor changes in certain scrapie strain-mouse strain combinations (Carp et al, 1984;Carp & Callahan, 1984) have established the importance of the genetic characteristics of host and agent, the role of the hypothalamus (Kim et al, 1987 a) and more recently the function of the adrenal gland in the weight increase (Kim et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Scrapie-induced Alterations in Glucose Tolerance in Mice

Carp

Kim²,

Callahan³

1989

Journal of General Virology

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SUMMARYCertain scrapie strains cause obesity in several strains of mice. The potential association between obesity and altered glucose tolerance was assessed by monitoring body weight and glucose tolerance throughout the incubation period in scrapie strainmouse strain combinations that do and do not produce obesity. Virtually all obese mice showed reduced glucose tolerance as shown by significantly higher blood glucose levels 2 h after a glucose overload. Mice injected with a scrapie strain that did not cause obesity showed normal tolerance. The scrapie infectivity titre of the pancreas of obese mice clinically affected with scrapie was very low. Adrenalectomy prevented both the increase in weight and aberrant glucose tolerance but had no other effect on the course of the disease. Following increasing dilution of the inoculum, the increase in body weight and the development of aberrant glucose tolerance reached an end-point that was similar to that of scrapie infectivity. The system described provides an inducible model of obesity with altered glucose tolerance.

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Adrenal Involvement in Scrapie-Induced Obesity

Abstract: In previous studies we found an increase in body weight during the preclinical phase 21

Cited by 37 publications

References 7 publications

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases

Scrapie-induced Alterations in Glucose Tolerance in Mice

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