TY - JOUR
T1 - Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation
T2 - A Human Randomized Crossover Trial
AU - Rittig, Nikolaj
AU - Bach, Ermina
AU - Thomsen, Henrik Holm
AU - Pedersen, Steen Bønlykke
AU - Nielsen, Thomas Svava
AU - Jørgensen, Jens O
AU - Jessen, Niels
AU - Møller, Niels
PY - 2016/9
Y1 - 2016/9
N2 - Background: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure. Methods: Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i) bolus injection of saline (Placebo) and ii) bolus injection of lipopolysaccharide endotoxin (LPS). A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. Results: LPS caused a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, p<0.001), a mean increase in lipid oxidation of 49% (CI-95%: 1-96, p = 0.047), and a median increase in energy expenditure of 28% (CI-95%: 16-42, p = 0.001) compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL) at ser650 in adipose tissue (p = 0.03), a trend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p = 0.09). Phosphatase and tensin homolog (PTEN) also tended to increase (p = 0.08) while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09) during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58. Conclusion: LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute inflammation and sepsis.
AB - Background: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure. Methods: Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i) bolus injection of saline (Placebo) and ii) bolus injection of lipopolysaccharide endotoxin (LPS). A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. Results: LPS caused a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, p<0.001), a mean increase in lipid oxidation of 49% (CI-95%: 1-96, p = 0.047), and a median increase in energy expenditure of 28% (CI-95%: 16-42, p = 0.001) compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL) at ser650 in adipose tissue (p = 0.03), a trend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p = 0.09). Phosphatase and tensin homolog (PTEN) also tended to increase (p = 0.08) while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09) during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58. Conclusion: LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute inflammation and sepsis.
KW - Journal Article
U2 - 10.1371/journal.pone.0162167
DO - 10.1371/journal.pone.0162167
M3 - Journal article
C2 - 27627109
SN - 1932-6203
VL - 11
SP - 1
EP - 13
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 9
M1 - e0162167
ER -