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Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

Heimann E, Nyman M, Degerman E - Adipocyte (2014)

Bottom Line: In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis.To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes.Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science; Lund University ; Lund, Sweden.

ABSTRACT
Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Short-chain fatty acids inhibit de novo lipogenesis in primary rat adipocytes. De novo lipogenesis was measured after 30 min of stimulation with or without 1 nM insulin (INS) in the presence or absence of 1, 3 and 10 mM propionic acid (PA) (A and B) or butyric acid (C and D). In A and C, the values are related to BASAL, condition without insulin and SCFA. In B and D, the values for PA and BA are related to CTRL (BASAL and INS are used as CTRL in respective group), either in a basal or an insulin-stimulated state. Mean ± SD (n = 3–6) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.
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f0002: Short-chain fatty acids inhibit de novo lipogenesis in primary rat adipocytes. De novo lipogenesis was measured after 30 min of stimulation with or without 1 nM insulin (INS) in the presence or absence of 1, 3 and 10 mM propionic acid (PA) (A and B) or butyric acid (C and D). In A and C, the values are related to BASAL, condition without insulin and SCFA. In B and D, the values for PA and BA are related to CTRL (BASAL and INS are used as CTRL in respective group), either in a basal or an insulin-stimulated state. Mean ± SD (n = 3–6) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.

Mentions: The effect of propionic acid and butyric acid on de novo lipogenesis was studied in primary rat adipocytes. It is well established that insulin stimulates the synthesis of fatty acids from e.g. glucose intermediates, known as de novo lipogenesis.21 As shown in Figure 2, both basal and insulin-stimulated de novo lipogenesis were inhibited by propionic acid and butyric acid, significant inhibition was seen at the lowest concentration (1 mM). To identify the molecular mechanism behind the inhibiting effect of SCFA, we studied the key enzyme ACC1 in de novo lipogenesis. In Figure 3, we show that propionic acid and butyric acid increased phosphorylation of ACC1 at serine 79. This leads to an inactivation of the enzymatic activity of ACC1.22 Taken together, the effect of propionic acid and butyric acid on phosphorylation of ACC1 is consistent with our finding that SCFA inhibits de novo lipogenesis.Figure 2.


Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

Heimann E, Nyman M, Degerman E - Adipocyte (2014)

Short-chain fatty acids inhibit de novo lipogenesis in primary rat adipocytes. De novo lipogenesis was measured after 30 min of stimulation with or without 1 nM insulin (INS) in the presence or absence of 1, 3 and 10 mM propionic acid (PA) (A and B) or butyric acid (C and D). In A and C, the values are related to BASAL, condition without insulin and SCFA. In B and D, the values for PA and BA are related to CTRL (BASAL and INS are used as CTRL in respective group), either in a basal or an insulin-stimulated state. Mean ± SD (n = 3–6) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496978&req=5

f0002: Short-chain fatty acids inhibit de novo lipogenesis in primary rat adipocytes. De novo lipogenesis was measured after 30 min of stimulation with or without 1 nM insulin (INS) in the presence or absence of 1, 3 and 10 mM propionic acid (PA) (A and B) or butyric acid (C and D). In A and C, the values are related to BASAL, condition without insulin and SCFA. In B and D, the values for PA and BA are related to CTRL (BASAL and INS are used as CTRL in respective group), either in a basal or an insulin-stimulated state. Mean ± SD (n = 3–6) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.
Mentions: The effect of propionic acid and butyric acid on de novo lipogenesis was studied in primary rat adipocytes. It is well established that insulin stimulates the synthesis of fatty acids from e.g. glucose intermediates, known as de novo lipogenesis.21 As shown in Figure 2, both basal and insulin-stimulated de novo lipogenesis were inhibited by propionic acid and butyric acid, significant inhibition was seen at the lowest concentration (1 mM). To identify the molecular mechanism behind the inhibiting effect of SCFA, we studied the key enzyme ACC1 in de novo lipogenesis. In Figure 3, we show that propionic acid and butyric acid increased phosphorylation of ACC1 at serine 79. This leads to an inactivation of the enzymatic activity of ACC1.22 Taken together, the effect of propionic acid and butyric acid on phosphorylation of ACC1 is consistent with our finding that SCFA inhibits de novo lipogenesis.Figure 2.

Bottom Line: In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis.To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes.Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science; Lund University ; Lund, Sweden.

ABSTRACT
Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus