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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 lipolysis in primary rat adipocytes. Lipolysis was measured after 30 min of stimulation with or without 30 nM isoproterenol (ISO), 10–30 U/ml adenosine deaminase (ADA) and 10 μM OPC3911 in the presence or absence of 3 and 10 mM propionic acid (PA) (A, B and E) or butyric acid (BA) (C-E). In A, C and E, the values are related to BASAL CTRL (condition without lipolytic agent and SCFA). In B and D, the values for PA and BA are related to respective CTRL (control without PA or BA) for each lipolytic condition. Mean ± SD (n = 5–13) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.
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f0001: Short-chain fatty acids inhibit lipolysis in primary rat adipocytes. Lipolysis was measured after 30 min of stimulation with or without 30 nM isoproterenol (ISO), 10–30 U/ml adenosine deaminase (ADA) and 10 μM OPC3911 in the presence or absence of 3 and 10 mM propionic acid (PA) (A, B and E) or butyric acid (BA) (C-E). In A, C and E, the values are related to BASAL CTRL (condition without lipolytic agent and SCFA). In B and D, the values for PA and BA are related to respective CTRL (control without PA or BA) for each lipolytic condition. Mean ± SD (n = 5–13) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.

Mentions: The effects of propionic acid and butyric acid on basal and stimulated lipolysis were studied in primary rat adipocytes. Adenosine deaminase (ADA), isoproterenol (ISO) and the cyclic nucleotide phosphodiesterase (PDE) 3 inhibitor OPC3911 were used to increase cAMP concentrations by different mechanisms, leading to activation of cAMP-dependent protein kinase A (PKA) and activation of hormone-sensitive lipase (HSL), which together with other proteins stimulate lipolysis.19 The PDE3 inhibitor is also used in order to test whether SCFAs mediate anti-lipolytic effects via the same pathway as insulin, which utilizes activation of PDE3B as a key component to inhibit lipolysis.20 As shown in Figure 1A and C, the presence of propionic acid or butyric acid, inhibit lipolysis stimulated via activation of the stimulatory G protein (Gs) by ISO, removal of the adenosine inhibitory effect on cAMP production by ADA or inhibition of cAMP degradation by the family-selective PDE3 inhibitor. However, the SCFAs did not have an effect on basal lipolysis. A significant inhibition of ADA-stimulated lipolysis was seen at 3 mM for propionic acid whereas 10 mM of either propionic acid or butyric acid were required for a significant inhibition of ADA- and ISO-stimulated lipolysis, as seen in Figure. 1B and D. “In the presence of OPC3911, basal as well as ISO-stimulated lipolysis was significantly enhanced (Fig. 1E). Furthermore, OPC3911 did not prevent the anti-lipolytic effect of propionic acid and butyric acid on ISO-stimulated lipolysis (Fig. 1F).Figure 1.


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 lipolysis in primary rat adipocytes. Lipolysis was measured after 30 min of stimulation with or without 30 nM isoproterenol (ISO), 10–30 U/ml adenosine deaminase (ADA) and 10 μM OPC3911 in the presence or absence of 3 and 10 mM propionic acid (PA) (A, B and E) or butyric acid (BA) (C-E). In A, C and E, the values are related to BASAL CTRL (condition without lipolytic agent and SCFA). In B and D, the values for PA and BA are related to respective CTRL (control without PA or BA) for each lipolytic condition. Mean ± SD (n = 5–13) 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

f0001: Short-chain fatty acids inhibit lipolysis in primary rat adipocytes. Lipolysis was measured after 30 min of stimulation with or without 30 nM isoproterenol (ISO), 10–30 U/ml adenosine deaminase (ADA) and 10 μM OPC3911 in the presence or absence of 3 and 10 mM propionic acid (PA) (A, B and E) or butyric acid (BA) (C-E). In A, C and E, the values are related to BASAL CTRL (condition without lipolytic agent and SCFA). In B and D, the values for PA and BA are related to respective CTRL (control without PA or BA) for each lipolytic condition. Mean ± SD (n = 5–13) were used and significance levels were accepted when *P < 0.05, **P < 0.01 and ***P < 0.001.
Mentions: The effects of propionic acid and butyric acid on basal and stimulated lipolysis were studied in primary rat adipocytes. Adenosine deaminase (ADA), isoproterenol (ISO) and the cyclic nucleotide phosphodiesterase (PDE) 3 inhibitor OPC3911 were used to increase cAMP concentrations by different mechanisms, leading to activation of cAMP-dependent protein kinase A (PKA) and activation of hormone-sensitive lipase (HSL), which together with other proteins stimulate lipolysis.19 The PDE3 inhibitor is also used in order to test whether SCFAs mediate anti-lipolytic effects via the same pathway as insulin, which utilizes activation of PDE3B as a key component to inhibit lipolysis.20 As shown in Figure 1A and C, the presence of propionic acid or butyric acid, inhibit lipolysis stimulated via activation of the stimulatory G protein (Gs) by ISO, removal of the adenosine inhibitory effect on cAMP production by ADA or inhibition of cAMP degradation by the family-selective PDE3 inhibitor. However, the SCFAs did not have an effect on basal lipolysis. A significant inhibition of ADA-stimulated lipolysis was seen at 3 mM for propionic acid whereas 10 mM of either propionic acid or butyric acid were required for a significant inhibition of ADA- and ISO-stimulated lipolysis, as seen in Figure. 1B and D. “In the presence of OPC3911, basal as well as ISO-stimulated lipolysis was significantly enhanced (Fig. 1E). Furthermore, OPC3911 did not prevent the anti-lipolytic effect of propionic acid and butyric acid on ISO-stimulated lipolysis (Fig. 1F).Figure 1.

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