2005

J Anim Sci. 2005 May;83(5):1023-32.
Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse.
Buff PR, Morrison CD, Ganjam VK, Keisler DH.
Department of Animal Sciences, University of Missouri, Columbia, 65211, USA.

Leptin is a protein hormone produced by adipose tissue that influences hypothalamic mechanisms regulating appetite and energy balance. In species tested thus far, including horses, concentrations of leptin increase as animal fat mass increases. The variables and mechanisms that influence the secretion of leptin are not well known, nor is it known in equine species how the secretion of leptin is influenced by acute alterations in energy balance, circadian patterns, and/or reproductive competence. Our objectives were to determine in horses: 1) whether plasma concentrations of leptin are secreted in a circadian and/or a pulsatile pattern; 2) whether a 48-h period of feed restriction would alter plasma concentrations of leptin, growth hormone, or insulin; and 3) whether ovariectomy and/or a melatonin implant would affect leptin. In Exp. 1, mares exposed to ambient photoperiod of visible light (11 h, 33 min to 11 h, 38 min), received treatments consisting of a 48-h feed restriction (RES) or 48 h of alfalfa hay fed ad libitum (FED). Mares were maintained in a dry lot before sampling and were tethered to a rail during sampling. Analyses revealed that leptin was not secreted in a pulsatile manner, and that mean leptin concentrations were greater (P < 0.001) in FED vs. RES mares (17.20 +/- 0.41 vs. 7.29 +/- 0.41 ng/mL). Plasma growth hormone was pulsatile, and mean concentrations were greater in RES than FED mares (2.15 +/- 0.31 vs. 1.08 +/- 0.31 ng/mL; P = 0.05). Circadian patterns of leptin secretion were observed, but only in FED mares (15.39 +/- 0.58 ng/mL for morning vs. 19.00 +/- 0.58 ng/mL for evening; P < 0.001). In Exp. 2, mares that were ovariectomized or intact received either a s.c. melatonin implant or a sham implant. Thereafter, blood was sampled at weekly intervals at 1000 and 1700. Concentrations of leptin in samples collected at 1700 were greater (P < 0.001) than in those collected at 1000 (28.24 +/- 1.7 vs. 22.07 +/- 1.7 ng/mL). Neither ovariectomy nor chronic treatment with melatonin affected plasma concentrations of leptin or the circadian pattern of secretion. These data provide evidence that plasma leptin concentrations in the equine are sensitive to acute changes in nutritional status and vary in a circadian pattern that is sensitive to fasting but not to melatonin treatment or ovariectomy.

Physiol Biochem Zool. 2005 Jan-Feb;78(1):90-104.
Ducklings exhibit substantial energy-saving mechanisms as a response to short-term food shortage.
Moe B, Stolevik E, Bech C.
Department of Biology, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.

We investigated whether Pekin ducklings (Anas platyrhyncos domesticus) exhibited any energy-saving mechanisms that could lessen the detrimental effects of reduced food intake during early development. Further, we evaluated the role of body compositional changes behind such potential mechanisms and the consequences on thermoregulatory capacity. The ducklings exhibited substantial energy-saving mechanisms as a response to diet restriction. After 5 d of diet restriction, the resting metabolic rate (RMR) of 10- and 20-d-old ducklings was 16.4% and 32.1% lower, respectively, than predicted from body mass compared with ad lib. fed ducklings (controls). These reductions in RMR could have been adaptive responses in anticipation of a lasting food shortage, or they could have been consequences of the restricted diet and the lack of essential nutrients. We argue that the responses were adaptive. The low RMRs were not a consequence of depleted fuel stores because the diet-restricted ducklings exhibited substantial amounts of stored lipids at the end of the diet-restriction periods. Hypothermia accounted for approximately 50% of the reduction in RMR in the 10-d-old diet-restricted ducklings, but hypothermia did not occur in the 20-d-old diet-restricted ducklings. Diet restriction resulted in a reduced liver and intestine size and an unchanged size of the leg muscles and heart, while the length of the skull increased (compared with controls of a given body mass). However, changes in body composition were only minor predictors of the observed changes in RMR. Peak metabolic rate (PMR) was approximately 10% lower in the diet-restricted ducklings compared with the controls. We have interpreted the lower PMR as a consequence of the reductions in RMR rather than as a consequence of a decreased function of the thermoregulatory effector mechanisms.

2003

Nature. 2003 May 8;423(6936):181-5
Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.
Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA.
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

2002

J Am Vet Med Assoc. 2002 May 1;220(9):1315-20
Effects of diet restriction on life span and age-related changes in dogs.
Kealy RD, Lawler DE, Ballam JM, Mantz SL, Biery DN, Greeley EH, Lust G, Segre M, Smith GK, Stowe HD.
Pet Nutrition Research Department, Nestle Purina Pet Care Co, St Louis, MO 63164, USA.

OBJECTIVE: To evaluate the effects of 25% diet restriction on life span of dogs and on markers of aging. DESIGN: Paired feeding study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair-mate from 8 weeks of age until death. Serum biochemical analyses were performed, body condition was scored, and body composition was measured annually until 12 years of age. Age at onset of chronic disease and median (age when 50% of the dogs were deceased) and maximum (age when 90% of the dogs were deceased) life spans were evaluated. RESULTS: Compared with control dogs, food-restricted dogs weighed less and had lower body fat content and lower serum triglycerides, triiodothyronine, insulin, and glucose concentrations. Median life span was significantly longer for dogs in which food was restricted. The onset of clinical signs of chronic disease generally was delayed for food-restricted dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that 25% restriction in food intake increased median life span and delayed the onset of signs of chronic disease in these dogs.