Effect of Central Corticotropin-Releasing Factor on Hepatic Lipid Metabolism and Inflammation-Related Gene Expression in Rats.

Yukiomi Nakade,Kazumasa Sakamoto,Yuji Kobayashi,Tadahisa Inoue,Satoshi Kimoto,Taeko Yamauchi,Masashi Yoneda,Kiyoaki Ito,Tomohiko Ohashi,Rena Kitano,Yoshio Sumida

doi:10.3390/ijms22083940

Yukiomi Nakade, Kazumasa Sakamoto + Show 9 more

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https://doi.org/10.3390/ijms22083940

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Abstract

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

Highlights

Converging neuroanatomical and neuropharmacological evidence suggests that central and autonomic nervous systems participate in the regulation of hepatic functions [1,2].The involvement of neurotransmitters mediating these effects in the central nervous system remains poorly understood
6 h and 24 h after intracisternal corticotropin-releasing factor (CRF) administration, hepatic sterol regulatory element-binding transcription factor 1 (SREBF1) mRNA levels increased significantly when compared with those observed in the control (Figure 1A)
We showed that intracisternally administered CRF augmen

Summary

Introduction

Converging neuroanatomical and neuropharmacological evidence suggests that central and autonomic nervous systems participate in the regulation of hepatic functions [1,2]. The involvement of neurotransmitters mediating these effects in the central nervous system remains poorly understood. Neuropeptides are recognized as neurotransmitters in the central and peripheral nervous systems [3,4]. Central acting neuropeptides regulate a variety of physiological functions. The effect of corticotropin-releasing factor (CRF) in the brain on the physiological and pathophysiological regulation of the gastrointestinal tract has been reported [5]. With regard to the gastrointestinal tract, central injection of CRF inhibited gastric motility and enhanced colonic motility through the parasympathetic vagal dependent cholinergic pathway in rats [6]

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