Abstract
High-fat-diet (HFD) feeding induces adipose dysfunction. This study aims to explore whether the Traditional Chinese Medical prescription Er-Miao-Fang could ameliorate adipose dysfunction and prevent hepatic glucose output. Short-term HFD feeding induced adipose lipolysis accompanied with enhanced hepatic glucose output in mice. Adipose lipolysis is initiated by cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling. Oral administration Er-Miao-Fang inhibited inflammation in adipose tissue by dephosphorylation of JNK and reducing TNF-α and IL-1β production, and thus preserved phosphodiesterase 3B (PDE3B) induction, contributing to preventing cAMP accumulation. As a result, from suppression of PKA activation, Er-Miao-Fang reduced fatty acids and glycerol release from adipose tissue due to the inhibition hormone-sensitive lipase (HSL). By blocking the traffic of fatty acids and inflammatory mediators from adipose tissue to the liver, Er-Miao-Fang attenuated hepatic cAMP/PKA signaling by protecting phosphodiesterase 4B (PDE4B) induction from inflammatory insult, and thereby reduced hepatic glucose production by suppression of hepatic glucagon response in HFD-fed mice. In conclusion, Er-Miao-Fang prevented adipose lipolysis by suppression of inflammation, contributing to reducing excessive hepatic glucose output. These findings present a new view of regulating gluconeogenesis and provide the guiding significance for the regulation of multi-link targets with Traditional Chinese Medicine.
Highlights
Adipose tissue functions as a site of fat storage, while adipose dysfunction in obesity and diabetes induces lipolysis and increases circulating free fatty acids to promote ectopic fat deposits
Short-term HFD feeding induced lipolysis from adipose tissue in mice, demonstrated by increased free fatty acids and glycerol released from isolated epididymal adipose tissue, whereas the increased lipolysis was inhibited by oral administration of Er-Miao-Fang extracts during HFD feeding (Figures 1A,B)
Because adipose lipolysis is mediated by cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, we examined the effects of Er-Miao-Fang in adipose tissue, and found that HFD feeding increased cAMP accumulation with reducing AMP contents in adipose tissue, whereas the changes were reversed by oral administration of Er-Miao-Fang (Figures 1C,D)
Summary
Adipose tissue functions as a site of fat storage, while adipose dysfunction in obesity and diabetes induces lipolysis and increases circulating free fatty acids to promote ectopic fat deposits. Er-Miao-Fang Prevents Hepatic Gluconeogenesis in liver is to suppress hepatic glucose production and lipolysisinduced lipid accumulation in the liver is shown to attenuate insulin sensitivity and increase hepatic glucose production, responsible for hyperglycemia during fasting in diabetes (Perry et al, 2014). These events suggest the functional interaction between adipose lipolysis and abnormal hepatic gluconeogenesis. Hepatic glucagon response is restrained by blocking cAMP/PKA signaling and inhibiting transcriptional regulation of G6Pase and PEPCK (He et al, 2009). All these well elucidate that cAMP/PKA signaling plays a vital role in regulation of lipid and glucose metabolism
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