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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) of rats remained reduced on the seventh day of continuous infusion with nesfatin-1. Increases in locomotor activity were also observed in nesfatin-1 treated animals (beam breaks/12 h; C–F) during the seventh day of continuous 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, and **P < 0.01 compared to controls.
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Figure 3: Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) of rats remained reduced on the seventh day of continuous infusion with nesfatin-1. Increases in locomotor activity were also observed in nesfatin-1 treated animals (beam breaks/12 h; C–F) during the seventh day of continuous 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, and **P < 0.01 compared to controls.

Mentions: On the last day (day 7) of continuous infusion of nesfatin-1, cumulative food intake during the dark phase was significantly reduced compared to the controls (Figure 3A). Similar to the short-term study, the average size of feeding bouts was significantly smaller in nesfatin-1 treated animals compared to controls during the dark phase (Figure 3B). Total activity (XTOT + ZTOT) remained significantly higher (~32%) for nesfatin-1 treated animals compared to saline treated controls (Figure 3C). Similarly, total ambulatory activity (XAMB) on the seventh day of infusion remained higher (~56%) in nesfatin-1 treated rats than control rats (Figure 3D). Nesfatin-1 treated rats experienced higher (~32%) than control nocturnal total horizontal activity on the seventh day of continuous infusion (Figure 3E). The number of dark phase feeding bouts of nesfatin-1 treated rats was not different than saline control rats on the seventh day of infusion (Supplemental Figure 2A). No differences were found in the water intake (Supplemental Figure 2B), total vertical activity (Figure 3F), and body weight (Supplemental Figure 2C) of saline treated and nesfatin-1 treated rats after 7 days of chronic infusion.


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) of rats remained reduced on the seventh day of continuous infusion with nesfatin-1. Increases in locomotor activity were also observed in nesfatin-1 treated animals (beam breaks/12 h; C–F) during the seventh day of continuous 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, and **P < 0.01 compared to controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Cumulative food intake (mg/g BW; A) and average feeding bout size (mg/g BW; B) of rats remained reduced on the seventh day of continuous infusion with nesfatin-1. Increases in locomotor activity were also observed in nesfatin-1 treated animals (beam breaks/12 h; C–F) during the seventh day of continuous 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, and **P < 0.01 compared to controls.
Mentions: On the last day (day 7) of continuous infusion of nesfatin-1, cumulative food intake during the dark phase was significantly reduced compared to the controls (Figure 3A). Similar to the short-term study, the average size of feeding bouts was significantly smaller in nesfatin-1 treated animals compared to controls during the dark phase (Figure 3B). Total activity (XTOT + ZTOT) remained significantly higher (~32%) for nesfatin-1 treated animals compared to saline treated controls (Figure 3C). Similarly, total ambulatory activity (XAMB) on the seventh day of infusion remained higher (~56%) in nesfatin-1 treated rats than control rats (Figure 3D). Nesfatin-1 treated rats experienced higher (~32%) than control nocturnal total horizontal activity on the seventh day of continuous infusion (Figure 3E). The number of dark phase feeding bouts of nesfatin-1 treated rats was not different than saline control rats on the seventh day of infusion (Supplemental Figure 2A). No differences were found in the water intake (Supplemental Figure 2B), total vertical activity (Figure 3F), and body weight (Supplemental Figure 2C) of saline treated and nesfatin-1 treated rats after 7 days of chronic infusion.

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