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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

Respiratory quotient (A) and relative contribution of fatty acids (B) and carbohydrates (C) to energy expenditure was not altered on day 7 of continuous infusion of nesfatin-1. However, the effect of nesfatin-1 on average O2 consumption (D), CO2 production (E), and energy expenditure (F) was reduced during the light phase of the seventh treatment day. The dark cycle in each panel occurred from 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. Data are represented as means ± SEM with an n = 4 rats/group. *P < 0.05, **P < 0.01 compared to control.
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Figure 4: Respiratory quotient (A) and relative contribution of fatty acids (B) and carbohydrates (C) to energy expenditure was not altered on day 7 of continuous infusion of nesfatin-1. However, the effect of nesfatin-1 on average O2 consumption (D), CO2 production (E), and energy expenditure (F) was reduced during the light phase of the seventh treatment day. The dark cycle in each panel occurred from 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. Data are represented as means ± SEM with an n = 4 rats/group. *P < 0.05, **P < 0.01 compared to control.

Mentions: The RQ of nesfatin-1 treated rats were not different from control rats at the end of the 7-day-nesfatin-1-infusion period (Figure 4A). The relative contribution of either carbohydrates or fatty acids toward energy production in nesfatin-1 treated rats was not statistically different between groups on the seventh day of the infusion period (Figures 4B,C). Interestingly, both average O2 consumption and average CO2 production decreased during the light phase for nesfatin-1 treated rats during the seventh day of infusion (Figures 4D,E). We observed a significant reduction in energy expenditure during the light phase in nesfatin-1-treated animals (Figure 4F) compared to saline treated controls. However, the total energy expenditure of nesfatin-1 treated rats during the dark phase was same as in control rats (Figure 4F).


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)

Respiratory quotient (A) and relative contribution of fatty acids (B) and carbohydrates (C) to energy expenditure was not altered on day 7 of continuous infusion of nesfatin-1. However, the effect of nesfatin-1 on average O2 consumption (D), CO2 production (E), and energy expenditure (F) was reduced during the light phase of the seventh treatment day. The dark cycle in each panel occurred from 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. Data are represented as means ± SEM with an n = 4 rats/group. *P < 0.05, **P < 0.01 compared to control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Respiratory quotient (A) and relative contribution of fatty acids (B) and carbohydrates (C) to energy expenditure was not altered on day 7 of continuous infusion of nesfatin-1. However, the effect of nesfatin-1 on average O2 consumption (D), CO2 production (E), and energy expenditure (F) was reduced during the light phase of the seventh treatment day. The dark cycle in each panel occurred from 1900 to 0700 h, while the light cycle was from 0700 to 1900 h next day. Data are represented as means ± SEM with an n = 4 rats/group. *P < 0.05, **P < 0.01 compared to control.
Mentions: The RQ of nesfatin-1 treated rats were not different from control rats at the end of the 7-day-nesfatin-1-infusion period (Figure 4A). The relative contribution of either carbohydrates or fatty acids toward energy production in nesfatin-1 treated rats was not statistically different between groups on the seventh day of the infusion period (Figures 4B,C). Interestingly, both average O2 consumption and average CO2 production decreased during the light phase for nesfatin-1 treated rats during the seventh day of infusion (Figures 4D,E). We observed a significant reduction in energy expenditure during the light phase in nesfatin-1-treated animals (Figure 4F) compared to saline treated controls. However, the total energy expenditure of nesfatin-1 treated rats during the dark phase was same as in control rats (Figure 4F).

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