Behavioral specificity of effects of 2-Mercaptoacetate on independent ingestion in developing rats

Swithers, Susan E.; Peters, Rebecca L.; Shin, Hans S.

doi:10.1002/(sici)1098-2302(199903)34:2<101::aid-dev3>3.0.co;2-j

Cited by 11 publications

(5 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decrease in postnatal body weight is also due to increased energy expenditure (20,64) and disinhibition of nonshivering thermogenesis (10,42), caused by leptin's stimulation of the sympathetic nervous system (10,20,42,64). No postnatal role for a decrease in energy intake due to altered ingestive behavior has been assigned so far (36,52,64). Further, no changes in hypothalamic neuropeptide expression were found in response to systemic leptin (3).…”

Section: Discussionmentioning

confidence: 99%

“…Despite previously detected changes in hypothalamic neuropeptides due to systemic leptin, no change in postnatal milk ingestion at 5-10 days of age was reported (36). However, milk ingestion assessments involved separation of pups from the mother and measuring pre-and postprandial pup weights after the pups ingested milk from blotting papers placed below them (36,52). Thus it is difficult to know whether the milk ingested was accurately measured.…”

Section: Discussionmentioning

confidence: 99%

“…Thus it is difficult to know whether the milk ingested was accurately measured. This is a universal limitation to postnatal studies where pup weights are used as a surrogate for milk ingestion (36,52). Even though postnatal leptin alters hypothalamic neuropeptides, these changes may predominantly perturb energy expenditure rather than energy intake between 10 and 15 days of age (20,64).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

Varma¹,

He²,

Shin³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

We investigated the effect of daily intracerebroventricular (ICV) leptin administration (neonatal age 2-7 days) on hypothalamic neuropeptides (neuropeptide Y, ␣-melanocyte-stimulating hormone) that regulate food intake, body weight (BW) gain, and the metabolic/hormonal profile in suckling (8 and 21 days) and adult rat (35, 60, 90, and 120 days). ICV leptin (0.16 g ⅐ g BW Ϫ1 ⅐ dose Ϫ1 ; n ϭ 70) led to a postnatal decline in BW (P ϭ 0.0002) that persisted only in the adult females (P ϭ 0.002). The postnatal decline in BW due to leptin was associated with a decline in food intake (P ϭ 0.01) and hypothalamic leptin receptor (P ϭ 0.008) and neuropeptide Y (P ϭ 0.008) immunoreactivities and an increase in ␣-melanocyte-stimulating hormone (P ϭ 0.008) immunoreactivity. In addition, hyperinsulinemia (P ϭ 0.01) with hypocorticosteronemia (P ϭ 0.007) occurred during the postnatal period with hypercorticosteronemia (P ϭ 0.007) and hypoleptinemia (P ϭ 0.008) and an increase in leutinizing hormone (P ϭ 0.01) in the adult male and female progeny. Persistent hyperinsulinemia (P ϭ 0.015) with hyperglycemia (P ϭ 0.008) and glucose intolerance (P ϭ 0.001) were observed only in the adult female. We conclude that postnatal leptin administration alters the adult female phenotype and speculate that this may relate to retention of leptin sensitivity resulting in a lipoatrophic state. development; ob gene; food intake; hyperinsulinemia; neuropeptide Y LEPTIN, THE TRANSLATED AND SECRETED PRODUCT of the ob gene (65), is primarily synthesized by adipose tissue (25), interacts with membrane-associated leptin receptors in various tissues (13,24,54), and regulates energy homeostasis by matching rates of energy expenditure with energy intake (25,42,45,46,61).The biological actions of leptin are composed of direct peripheral (on target organs) and central (via hypothalamic and sympathetic nervous system) effects. Peripherally, leptin affects the metabolism of various tissues including the pancreatic ␤-islets (30, 66), adipocytes (38, 42), skeletal muscle (50, 62), and liver (41), thereby modulating insulin secretion and sensitivity (30,41,42,50,62,66). Centrally, leptin traverses the blood-brain barrier via receptor-mediated transcytosis (ObRa) or, in the absence of a blood-brain barrier, directly accesses the intracellular signal-transducing long isoform of the leptin receptor (ObRb) expressed in the hypothalamus (2,6,8,54). In the hypothalamus, leptin alters the synthesis and release of key orexigenic (neuropeptide Y, agouti-related peptide) and anorexigenic (proopiomelanocortin and cocaine and amphetamine-related transcript) peptides in the adult, thereby suppressing appetite resulting in anorexia, increasing sympathetic nervous output resulting in enhanced energy expenditure, and ultimately producing weight loss (16,46,61).Although most of the studies involving leptin action have been reported in the adult, some information during the postnatal period exists. Circulating leptin concentrations peak in the suckling mouse at age 7-10 days and ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

Varma¹,

He²,

Shin³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…2‐Mercaptoacetate (the same compound as thioglycolate) is used as a metabolic inhibitor of fatty acid oxidation (Swithers, 2000) by blockage of acetyl‐CoA dehydrogenase (Bray, 2000). 2‐Mercaptoacetate stimulates feed intake through afferent signals to the central nervous system, which controls food seeking and satiety through changes in fatty acid oxidation in adult rats (Langhans and Scharrer, 1987; Stockinger and Geary, 1990; Singer et al, 1997; Ritter et al, 1999), in developing rats (Swithers et al, 1999; Swithers, 2000), and in mice (Del Prete et al, 1998). Subsequent altered ketogenesis also plays a role in alterations of feed intake (Scharrer, 1999).…”

Section: Discussionmentioning

confidence: 99%

Developmental toxicity evaluation of sodium thioglycolate administered topically to Sprague–Dawley (CD) rats and New Zealand white rabbits

Tyl

Price

Marr

et al. 2003

Birth Defects Research Pt B

View full text Add to dashboard Cite

BACKGROUND: Sodium thioglycolate, which has widespread occupational and consumer exposure to women from cosmetics and hair-care products, was evaluated for developmental toxicity by topical exposure during the embryonic and fetal periods of pregnancy METHODS: Timed-mated Sprague-Dawley rats (25/group) and New Zealand White (NZW) rabbits (24/group) were exposed to sodium thioglycolate in vehicle (95% ethanol:distilled water, 1:1) by unoccluded topical application on gestational days (GD) 6-19 (rats) or 6-29 (rabbits) for 6 hr/day, at 0, 50, 100, or 200 mg/kg body weight/day (rats) and 0, 10, 15, 25, or 65 mg/kg/day (rabbits). At termination (GD 20 rats; GD 30 rabbits), fetuses were examined for external, visceral, and skeletal malformations and variations. RESULTS: In rats, maternal topical exposure to sodium thioglycolate, at 200 mg/kg/day (the highest dose tested) on GD 6-19, resulted in maternal toxicity, including reduced body weights and weight gain, increased relative water consumption and one death. Treatmentrelated increases in feed consumption and changes at the application site occurred at all doses, in the absence of increased body weights or body weight change. Fetal body weights/litter were decreased at 200 mg/kg/day, with no other embryo/fetal toxicity and no treatment-related teratogenicity in any group. In rabbits, maternal topical exposure to sodium thioglycolate on GD 6-29 resulted in maternal dose-related toxicity at the dosing site in all groups; no maternal systemic toxicity, embryo/fetal toxicity, or treatment-related teratogenicity were observed in any group. CONCLUSIONS: A no observed adverse effect level (NOAEL) was not identified for maternal toxicity in either species with the dosages tested. The developmental toxicity NOAEL was 100 mg/kg/day (rats) and Z65 mg/kg/day (rabbits; the highest dose tested).

show abstract

“…For example, centrally acting dopamine receptor antagonists dose-dependently suppress intake of 10% sucrose from the floor in 7-day-old rats without affecting their overall activity, but those drugs do not inhibit sucrose intake from intraoral catheters (Tyrka & Smith, 1991;Tyrka, Gayle, & Smith, 1992). A similar behavioral dissociation has been reported in older pups after blockade of fatty acid oxidation using 2-mercaptoacetate (Swithers, Peters, & Shin, 1999).…”

Section: Independent Ingestion In Neonatal Ratsmentioning

confidence: 65%

Postnatal Development of Central Feeding Circuits

Rinaman

Neurobiology of Food and Fluid Intake

View full text Add to dashboard Cite

Behavioral specificity of effects of 2-Mercaptoacetate on independent ingestion in developing rats

Cited by 11 publications

References 14 publications

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

Developmental toxicity evaluation of sodium thioglycolate administered topically to Sprague–Dawley (CD) rats and New Zealand white rabbits

Postnatal Development of Central Feeding Circuits

Contact Info

Product

Resources

About