PMID- 25535832 OWN - NLM STAT- MEDLINE DCOM- 20150429 LR - 20150221 IS - 1945-7170 (Electronic) IS - 0013-7227 (Linking) VI - 156 IP - 3 DP - 2015 Mar TI - Acyl ghrelin acts in the brain to control liver function and peripheral glucose homeostasis in male mice. PG - 858-68 LID - 10.1210/en.2014-1733 [doi] AB - Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pair-fed or ad libitum feeding conditions. Mice received intracerebroventricular (icv) infusion of artificial cerebrospinal fluid (aCSF), ghrelin, and allowed to eat ad libitum (icv ghrelin ad lib) or ghrelin and pair-fed to the aCSF group (icv ghrelin pf). Minipumps delivered acyl ghrelin at a dose of 0.25 mug/h at 0.5 muL/h for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides, or nonesterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad lib mice. However, both icv ghrelin ad lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad lib mice during a glucose tolerance test, although both icv ghrelin ad lib and icv ghrelin pf increased insulin release during the glucose tolerance test. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf), central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis. FAU - Stark, Romana AU - Stark R AD - Department of Physiology (R.S., A.R., S.H.L., Q.W., Z.B.A.), Monash University, Clayton, Victoria 3800, Australia; Traditional Chinese Medicine Department (Q.W.), Peking Union Medical College Hospital, Dongcheng District, Beijing 100730, China; Department of Animal Physiology (C.P., A.T.), Faculty of Biology, Phillips University, D-35043 Marburg, Germany; and Department of Physiology (A.T.), Otago School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand. FAU - Reichenbach, Alex AU - Reichenbach A FAU - Lockie, Sarah H AU - Lockie SH FAU - Pracht, Corinna AU - Pracht C FAU - Wu, Qunli AU - Wu Q FAU - Tups, Alexander AU - Tups A FAU - Andrews, Zane B AU - Andrews ZB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141223 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Blood Glucose) RN - 0 (Ghrelin) RN - 0 (Insulin) RN - 0 (Leptin) RN - 8558G7RUTR (Pyruvic Acid) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Acylation MH - Animals MH - Blood Glucose/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Ghrelin/blood/*pharmacology MH - Glucose/*metabolism MH - Glucose Tolerance Test MH - Homeostasis/*drug effects MH - Insulin/blood/metabolism MH - Leptin/blood/metabolism MH - Liver/*drug effects/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Pyruvic Acid/metabolism EDAT- 2014/12/24 06:00 MHDA- 2015/04/30 06:00 CRDT- 2014/12/24 06:00 PHST- 2014/12/24 06:00 [entrez] PHST- 2014/12/24 06:00 [pubmed] PHST- 2015/04/30 06:00 [medline] AID - 10.1210/en.2014-1733 [doi] PST - ppublish SO - Endocrinology. 2015 Mar;156(3):858-68. doi: 10.1210/en.2014-1733. Epub 2014 Dec 23.