Limits...
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.

Show MeSH

Related in: MedlinePlus

Markers of skeletal muscle and liver energy expenditure and glucose storage. Ex vivo quadriceps muscle (A) glucose oxidation, (B) fatty acid oxidation and (C) fatty acid incorporation into diglyceride. Ex vivo liver (D) glycogen content, (E) glucose-6-phosphate content and (F) glucokinase activity. All values are presented as mean ± SEM for NI-IgG treated mice (n = 6, white bars) and Anti-ASP treated mice (n = 7, black bars), where* P < 0.05 and ** P < 0.01 analyzed by unpaired two-tailed t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2875207&req=5

Figure 3: Markers of skeletal muscle and liver energy expenditure and glucose storage. Ex vivo quadriceps muscle (A) glucose oxidation, (B) fatty acid oxidation and (C) fatty acid incorporation into diglyceride. Ex vivo liver (D) glycogen content, (E) glucose-6-phosphate content and (F) glucokinase activity. All values are presented as mean ± SEM for NI-IgG treated mice (n = 6, white bars) and Anti-ASP treated mice (n = 7, black bars), where* P < 0.05 and ** P < 0.01 analyzed by unpaired two-tailed t-test.

Mentions: Twenty-four hour energy expenditure was significantly elevated in Anti-ASP treated mice (P < 0.0001, Figure 2D). Analysis of dark and light 12-h cycles separately indicates a significant increase with anti-ASP for both time periods (P < 0.0001, 2-way ANOVA, AUC Figure 2E). While RQ increased with feeding (indicating increased glucose utilization during this period), there was no change in RQ in either dark or light cycles between the two groups, suggesting a whole body increase in both glucose and fatty acid oxidation (Figure 2F). To investigate the mechanism of augmented whole body energy expenditure, we evaluated glucose and fatty acid consumption in skeletal muscle and liver. In the skeletal muscle, glucose oxidation was significantly increased more than two-fold in Anti-ASP treated mice (P < 0.01, Figure 3A). On the other hand, palmitate oxidation was reduced (P < 0.05, Figure 3B) with a shift of palmitate from oxidation towards incorporation into diglycerides (P = 0.05, Figure 3C) with no change in TG incorporation or total TG mass (data not shown). In the liver, glycogen content was decreased by 34% (P < 0.05, Figure 3D) associated with a trend in reduced glucose-6-phosphate content (P = 0.08, Figure 3E) and no change in glucokinase (GK) activity (NS, Figure 3F). Also, there was no difference in liver TG mass (NI-IgG: 40.6 ± 4.6 μmoles/g and Anti-ASP: 43.0 ± 5.3 μmoles/g, NS, n = 5-7).


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)

Markers of skeletal muscle and liver energy expenditure and glucose storage. Ex vivo quadriceps muscle (A) glucose oxidation, (B) fatty acid oxidation and (C) fatty acid incorporation into diglyceride. Ex vivo liver (D) glycogen content, (E) glucose-6-phosphate content and (F) glucokinase activity. All values are presented as mean ± SEM for NI-IgG treated mice (n = 6, white bars) and Anti-ASP treated mice (n = 7, black bars), where* P < 0.05 and ** P < 0.01 analyzed by unpaired two-tailed t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Markers of skeletal muscle and liver energy expenditure and glucose storage. Ex vivo quadriceps muscle (A) glucose oxidation, (B) fatty acid oxidation and (C) fatty acid incorporation into diglyceride. Ex vivo liver (D) glycogen content, (E) glucose-6-phosphate content and (F) glucokinase activity. All values are presented as mean ± SEM for NI-IgG treated mice (n = 6, white bars) and Anti-ASP treated mice (n = 7, black bars), where* P < 0.05 and ** P < 0.01 analyzed by unpaired two-tailed t-test.
Mentions: Twenty-four hour energy expenditure was significantly elevated in Anti-ASP treated mice (P < 0.0001, Figure 2D). Analysis of dark and light 12-h cycles separately indicates a significant increase with anti-ASP for both time periods (P < 0.0001, 2-way ANOVA, AUC Figure 2E). While RQ increased with feeding (indicating increased glucose utilization during this period), there was no change in RQ in either dark or light cycles between the two groups, suggesting a whole body increase in both glucose and fatty acid oxidation (Figure 2F). To investigate the mechanism of augmented whole body energy expenditure, we evaluated glucose and fatty acid consumption in skeletal muscle and liver. In the skeletal muscle, glucose oxidation was significantly increased more than two-fold in Anti-ASP treated mice (P < 0.01, Figure 3A). On the other hand, palmitate oxidation was reduced (P < 0.05, Figure 3B) with a shift of palmitate from oxidation towards incorporation into diglycerides (P = 0.05, Figure 3C) with no change in TG incorporation or total TG mass (data not shown). In the liver, glycogen content was decreased by 34% (P < 0.05, Figure 3D) associated with a trend in reduced glucose-6-phosphate content (P = 0.08, Figure 3E) and no change in glucokinase (GK) activity (NS, Figure 3F). Also, there was no difference in liver TG mass (NI-IgG: 40.6 ± 4.6 μmoles/g and Anti-ASP: 43.0 ± 5.3 μmoles/g, NS, n = 5-7).

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