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The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice.

Paglialunga S, Fisette A, Munkonda M, Gao Y, Richard D, Cianflone K - BMC Physiol. (2010)

Bottom Line: Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake.Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, G1V 4G5, Canada.

ABSTRACT

Background: Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure.

Results: In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P < 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P < 0.0001), increased skeletal muscle glucose oxidation (+141%, P < 0.001), reduced liver glycogen (-34%, P < 0.05) and glucose-6-phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P < 0.0001) and increased body weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).

Conclusion: In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

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Related in: MedlinePlus

Effects of recombinant ASP treatment on plasma NEFA levels, body weight and food intake in wildtype mice. Fasting plasma samples from PBS treated mice (n = 6, white hatched bars) and rASP treated mice (n = 5, gray hatched bars). (A) Human rASP detected in mouse plasma following 9 days and 4 weeks treatment. (B) Fasting NEFA levels after 4 weeks treatment. Results were analyzed by unpaired two-tailed t-test. (C) Body weight (g) and (D) cumulative food intake (kcal) for PBS (n = 6, white circles) and rASP (n = 5, black circles) treated mice. Results were analyzed by two-way ANOVA. Group and Time P values are reported in graph. All values are presented as mean ± SEM, where * P < 0.05.
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Figure 4: Effects of recombinant ASP treatment on plasma NEFA levels, body weight and food intake in wildtype mice. Fasting plasma samples from PBS treated mice (n = 6, white hatched bars) and rASP treated mice (n = 5, gray hatched bars). (A) Human rASP detected in mouse plasma following 9 days and 4 weeks treatment. (B) Fasting NEFA levels after 4 weeks treatment. Results were analyzed by unpaired two-tailed t-test. (C) Body weight (g) and (D) cumulative food intake (kcal) for PBS (n = 6, white circles) and rASP (n = 5, black circles) treated mice. Results were analyzed by two-way ANOVA. Group and Time P values are reported in graph. All values are presented as mean ± SEM, where * P < 0.05.

Mentions: Next, we treated WT mice with human rASP for 4 weeks to enhance ASP action. Immunoreactive circulating human rASP was detected at ~0.3 pmol/mL on day 9 and remained constant until the end of the study period (Figure 4A). Interestingly, NEFA levels were significantly lower in the rASP treated mice (P < 0.05, Figure 3B). Fasting glucose levels were similar between rASP and PBS treated mice (PBS: 6.77 ± 0.74 and rASP: 6.81 ± 0.58 mmol/L, NS, n = 5-6). In addition, no difference in plasma TG, insulin or adiponectin were detected between PBS and rASP treated mice, however C3 levels were significantly elevated in the rASP treated mice (Table 2).


The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice.

Paglialunga S, Fisette A, Munkonda M, Gao Y, Richard D, Cianflone K - BMC Physiol. (2010)

Effects of recombinant ASP treatment on plasma NEFA levels, body weight and food intake in wildtype mice. Fasting plasma samples from PBS treated mice (n = 6, white hatched bars) and rASP treated mice (n = 5, gray hatched bars). (A) Human rASP detected in mouse plasma following 9 days and 4 weeks treatment. (B) Fasting NEFA levels after 4 weeks treatment. Results were analyzed by unpaired two-tailed t-test. (C) Body weight (g) and (D) cumulative food intake (kcal) for PBS (n = 6, white circles) and rASP (n = 5, black circles) treated mice. Results were analyzed by two-way ANOVA. Group and Time P values are reported in graph. All values are presented as mean ± SEM, where * P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875207&req=5

Figure 4: Effects of recombinant ASP treatment on plasma NEFA levels, body weight and food intake in wildtype mice. Fasting plasma samples from PBS treated mice (n = 6, white hatched bars) and rASP treated mice (n = 5, gray hatched bars). (A) Human rASP detected in mouse plasma following 9 days and 4 weeks treatment. (B) Fasting NEFA levels after 4 weeks treatment. Results were analyzed by unpaired two-tailed t-test. (C) Body weight (g) and (D) cumulative food intake (kcal) for PBS (n = 6, white circles) and rASP (n = 5, black circles) treated mice. Results were analyzed by two-way ANOVA. Group and Time P values are reported in graph. All values are presented as mean ± SEM, where * P < 0.05.
Mentions: Next, we treated WT mice with human rASP for 4 weeks to enhance ASP action. Immunoreactive circulating human rASP was detected at ~0.3 pmol/mL on day 9 and remained constant until the end of the study period (Figure 4A). Interestingly, NEFA levels were significantly lower in the rASP treated mice (P < 0.05, Figure 3B). Fasting glucose levels were similar between rASP and PBS treated mice (PBS: 6.77 ± 0.74 and rASP: 6.81 ± 0.58 mmol/L, NS, n = 5-6). In addition, no difference in plasma TG, insulin or adiponectin were detected between PBS and rASP treated mice, however C3 levels were significantly elevated in the rASP treated mice (Table 2).

Bottom Line: Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake.Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, G1V 4G5, Canada.

ABSTRACT

Background: Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure.

Results: In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P < 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P < 0.0001), increased skeletal muscle glucose oxidation (+141%, P < 0.001), reduced liver glycogen (-34%, P < 0.05) and glucose-6-phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P < 0.0001) and increased body weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).

Conclusion: In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

Show MeSH
Related in: MedlinePlus