American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Dec 2013
Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice.
Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A(y) mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. ⋯ However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Nov 2013
Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.
Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. ⋯ At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Nov 2013
Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition.
Mild decrease of core temperature (32-34°C), also known as therapeutic hypothermia, is a highly effective strategy of neuroprotection from ischemia and holds significant promise in the treatment of stroke. However, induction of hypothermia in conscious stroke patients is complicated by cold-defensive responses, such as shivering and tachycardia. Although multiple thermoregulatory responses may be altered by modulators of thermosensitive ion channels, TRPM8 (transient receptor potential melastatin 8) and TRPV1 (TRP vanilloid 1), it is unknown whether these agents affect cold-induced shivering and tachycardia. ⋯ DHC: 5.1 ± 2.0 V·s/min), tachycardia (ΔHR = 204 ± 25 vs. 3 ± 35 beats/min) and produced a profound drop in core temperature (-2.2 ± 0.6 vs. -8.9 ± 0.6°C). In conclusion, external cooling-induced shivering and tachycardia are suppressed by TRPV1 activation, but not by TRPM8 inhibition. This suggests that TRPV1 agonists may be combined with external physical cooling to achieve more rapid and effective hypothermia.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Oct 2013
Characterization of the development of renal injury in Type-1 diabetic Dahl salt-sensitive rats.
The present study compared the progression of renal injury in Sprague-Dawley (SD) and Dahl salt-sensitive (SS) treated with streptozotocin (STZ). The rats received an injection of STZ (50 mg/kg ip) and an insulin pellet (2 U/day sc) to maintain the blood glucose levels between 400 and 600 mg/dl. Twelve weeks later, arterial pressure (143 ± 6 vs. 107 ± 8 mmHg) and proteinuria (557 ± 85 vs. 81 ± 6 mg/day) were significantly elevated in STZ-SS rats compared with the values observed in STZ-SD rats, respectively. ⋯ Nine weeks after diabetes onset, there was a 42% increase in glomerular filtration rate in STZ-SS rats vs. time-control SS rats with reduced renal blood flow. These results indicate that SS rats treated with STZ develop hyperfiltration and progressive proteinuria and display renal histological lesions characteristic of those seen in patients with diabetic nephropathy. Overall, this model may be useful to study signaling pathways and mechanisms that play a role in the progression of diabetes-induced renal disease and the development of new therapies to slow the progression of diabetic nephropathy.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2013
Whole body heat loss is reduced in older males during short bouts of intermittent exercise.
Studies in young adults show that a greater proportion of heat is gained shortly following the start of exercise and that temporal changes in whole body heat loss during intermittent exercise have a pronounced effect on body heat storage. The consequences of short-duration intermittent exercise on heat storage with aging are unclear. We compared evaporative heat loss (HE) and changes in body heat content (ΔHb) between young (20-30 yr), middle-aged (40-45 yr), and older males (60-70 yr) of similar body mass and surface area, during successive exercise (4 × 15 min) and recovery periods (4 × 15 min) at a fixed rate of heat production (400 W) and under fixed environmental conditions (35 °C/20% relative humidity). ⋯ HE was not significantly different between groups during the recovery periods. The net effect over 2 h was a greater ΔHb in older (267 ± 33 kJ; P = 0.016) and middle-aged adults (245 ± 16 kJ; P = 0.073) relative to younger counterparts (164 ± 20 kJ). As a result of a reduced capacity to dissipate heat during exercise, which was not compensated by a sufficiently greater rate of heat loss during recovery, both older and middle-aged males had a progressively greater rate of heat storage compared with young males over 2 h of intermittent exercise.