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Long-term infusion of nesfatin-1 causes a sustained regulation of whole-body energy homeostasis of male Fischer 344 rats.

Mortazavi S, Gonzalez R, Ceddia R, Unniappan S - Front Cell Dev Biol (2015)

Bottom Line: Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects.On the seventh day of nesfatin-1 infusion, cumulative food intake, and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively.Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan Saskatoon, SK, Canada.

ABSTRACT
Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects. Nesfatin-1 has been proposed as a potential anti-obesity peptide. However, studies to date have mainly focused on the acute satiety effects of centrally administered nesfatin-1. The main objective of our studies was to characterize the long-term/chronic effects of peripheral administration of nesfatin-1 on whole-body energy balance and metabolic partitioning in male Fischer 344 rats. Short-term (1 day) subcutaneous infusion of nesfatin-1 (50 μg/kg body weight/day) using osmotic mini-pumps increased spontaneous physical activity and whole-body fat oxidation during the dark phase. This was accompanied by decreased food intake and basal metabolic rate compared to saline infused controls. On the seventh day of nesfatin-1 infusion, cumulative food intake, and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively. Meanwhile, intraperitoneal injection of nesfatin-1 only caused a dark phase specific reduction in food intake and an increase in physical activity. NUCB2 mRNA expression in the brain and stomach, as well as serum NUCB2 concentrations were significantly reduced after 24 h fasting, while a post-prandial increase in serum NUCB2 was found in ad libitum fed rats. Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

No MeSH data available.


Related in: MedlinePlus

Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) decreased in rats continuously infused with 50 μg/kg body weight/day nesfatin-1 for 1 day. An increase in locomotor activity (beam breaks/12 h; C–F) was also observed during the dark phase of nesfatin-1 infusion. The activities were presented as total horizontal (X-TOT), ambulatory (X-AMB, which refers to successive beam breaks in the X axis), and vertical (Z-TOT) movements. Dark cycle occurred during 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. All data are presented as means ± SEM with an n = 4 rats/group. *P < 0.05 compared to control.
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Figure 1: Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) decreased in rats continuously infused with 50 μg/kg body weight/day nesfatin-1 for 1 day. An increase in locomotor activity (beam breaks/12 h; C–F) was also observed during the dark phase of nesfatin-1 infusion. The activities were presented as total horizontal (X-TOT), ambulatory (X-AMB, which refers to successive beam breaks in the X axis), and vertical (Z-TOT) movements. Dark cycle occurred during 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. All data are presented as means ± SEM with an n = 4 rats/group. *P < 0.05 compared to control.

Mentions: When compared to controls, nesfatin-1 treatment elicited a significant reduction in cumulative food intake during the 12-h dark phase (Figure 1A). The average feeding bout size was significantly lower for nesfatin-1 treated animals compared to saline treated controls in both dark and light phases (Figure 1B). Total (Figure 1C), ambulatory (Figure 1D), horizontal (Figure 1E) and vertical (Figure 1E) activities of nesfatin-1 treated rats were significantly higher than control group during the dark phase. The spontaneous physical activity was not different in nesfatin-1-treated and control animals during the light phase (Figures 1C–F). The total number of feeding bouts was not significantly different between treated and untreated animals (Supplemental Figure 1A). No change in cumulative water intake was observed between nesfatin-1 treated and control animals (Supplemental Figure 1B). There were no significant differences in the body weight of nesfatin-1 treated and control animals (Supplemental Figure 1C).


Long-term infusion of nesfatin-1 causes a sustained regulation of whole-body energy homeostasis of male Fischer 344 rats.

Mortazavi S, Gonzalez R, Ceddia R, Unniappan S - Front Cell Dev Biol (2015)

Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) decreased in rats continuously infused with 50 μg/kg body weight/day nesfatin-1 for 1 day. An increase in locomotor activity (beam breaks/12 h; C–F) was also observed during the dark phase of nesfatin-1 infusion. The activities were presented as total horizontal (X-TOT), ambulatory (X-AMB, which refers to successive beam breaks in the X axis), and vertical (Z-TOT) movements. Dark cycle occurred during 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. All data are presented as means ± SEM with an n = 4 rats/group. *P < 0.05 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389570&req=5

Figure 1: Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) decreased in rats continuously infused with 50 μg/kg body weight/day nesfatin-1 for 1 day. An increase in locomotor activity (beam breaks/12 h; C–F) was also observed during the dark phase of nesfatin-1 infusion. The activities were presented as total horizontal (X-TOT), ambulatory (X-AMB, which refers to successive beam breaks in the X axis), and vertical (Z-TOT) movements. Dark cycle occurred during 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. All data are presented as means ± SEM with an n = 4 rats/group. *P < 0.05 compared to control.
Mentions: When compared to controls, nesfatin-1 treatment elicited a significant reduction in cumulative food intake during the 12-h dark phase (Figure 1A). The average feeding bout size was significantly lower for nesfatin-1 treated animals compared to saline treated controls in both dark and light phases (Figure 1B). Total (Figure 1C), ambulatory (Figure 1D), horizontal (Figure 1E) and vertical (Figure 1E) activities of nesfatin-1 treated rats were significantly higher than control group during the dark phase. The spontaneous physical activity was not different in nesfatin-1-treated and control animals during the light phase (Figures 1C–F). The total number of feeding bouts was not significantly different between treated and untreated animals (Supplemental Figure 1A). No change in cumulative water intake was observed between nesfatin-1 treated and control animals (Supplemental Figure 1B). There were no significant differences in the body weight of nesfatin-1 treated and control animals (Supplemental Figure 1C).

Bottom Line: Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects.On the seventh day of nesfatin-1 infusion, cumulative food intake, and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively.Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan Saskatoon, SK, Canada.

ABSTRACT
Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects. Nesfatin-1 has been proposed as a potential anti-obesity peptide. However, studies to date have mainly focused on the acute satiety effects of centrally administered nesfatin-1. The main objective of our studies was to characterize the long-term/chronic effects of peripheral administration of nesfatin-1 on whole-body energy balance and metabolic partitioning in male Fischer 344 rats. Short-term (1 day) subcutaneous infusion of nesfatin-1 (50 μg/kg body weight/day) using osmotic mini-pumps increased spontaneous physical activity and whole-body fat oxidation during the dark phase. This was accompanied by decreased food intake and basal metabolic rate compared to saline infused controls. On the seventh day of nesfatin-1 infusion, cumulative food intake, and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively. Meanwhile, intraperitoneal injection of nesfatin-1 only caused a dark phase specific reduction in food intake and an increase in physical activity. NUCB2 mRNA expression in the brain and stomach, as well as serum NUCB2 concentrations were significantly reduced after 24 h fasting, while a post-prandial increase in serum NUCB2 was found in ad libitum fed rats. Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

No MeSH data available.


Related in: MedlinePlus