Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Yukawa, Michi; Weigle, David S.; Davis, Charles D.; Marck, Brett T.; Wolden‐Hanson, Tami

doi:10.1152/ajpregu.00035.2008

Cited by 14 publications

(11 citation statements)

References 73 publications

(109 reference statements)

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“…In the present experiments, ipamorelin treatment of rats with POI improved body weight gain after surgery. Our finding is in agreement with the results of a recent study showing that postoperative ghrelin treatment decreased the production of proinflammatory cytokine interleukin-6 and stabilized the body weight in senescent rats after surgery (Yukawa et al, 2008). However, additional studies specifically designed to investigate the effect of ipamorelin on inflammatory cytokine production are required to confirm its anti-inflammatory action.…”

Section: Discussionsupporting

confidence: 93%

Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus

Venkova¹,

Mann²,

Nelson³

et al. 2009

J Pharmacol Exp Ther

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Ghrelin and ghrelin mimetics stimulate appetite and enhance gastric motility. The present study investigates whether ipamorelin, a selective growth hormone secretagogue and agonist of the ghrelin receptor, would accelerate gastrointestinal transit and ameliorate the symptoms in a rodent model of postoperative ileus (POI). Fasted male rats were subjected to laparotomy and intestinal manipulation. At the end of surgery, a dye marker was infused in the proximal colon to evaluate postsurgical colonic transit time, which was the time to the first bowel movement. In addition, fecal pellet output, food intake, and body weight were monitored regularly for 48 h. Ipamorelin (0.01-1 mg/kg), growth hormone-releasing peptide (GHRP)-6 (20 g/kg), or vehicle (saline) were administered via intravenous bolus infusion after a single dosing or a 2-day repetitive dosing regimen (four doses a day at 3-h intervals). Compared with the vehicle, a single dose of ipamorelin (1 mg/kg) or GHRP-6 (20 g/kg) decreased the time to the first bowel movement but had no effect on cumulative fecal output, food intake, or body weight gain measured 48 h after the surgery. In contrast, repetitive dosing of ipamorelin (0.1 or 1 mg/kg) significantly increased the cumulative fecal pellet output, food intake, and body weight gain. The results suggest that postsurgical intravenous infusions of ipamorelin may ameliorate the symptoms in patients with POI.Postoperative ileus (POI) is a gastrointestinal (GI) dysfunction that develops as a consequence of abdominal surgery or other major surgical procedures. Abdominal distention, nausea, vomiting, anorexia, and an inability to pass stool are the main symptoms of POI. Although normal GI motility returns spontaneously within several days in most patients, POI is the main cause for prolonged hospitalization and often leads to serious complications in others (Senagore, 2007). The mechanisms causing POI are complex, involving immune and neuronal reactions to the surgery that result in delayed gastric emptying and impaired propulsive motility of the bowel (Bauer and Boeckxstaens, 2004). In addition, opioid drugs used for pain management contribute significantly to the delay in GI transit.POI is a generalized event involving the entire GI tract and not restricted to the region directly subjected to manipulation. Manipulation of the small intestine in the rat was found to inhibit muscle contractility and evoke inflammatory responses in the stomach and the colon (Kalff et al., 1998;Schwarz et al., 2004), whereas manipulation of the cecum delayed gastric emptying (Martínez et al., 1999). Moreover, the time course of functional recovery varies in different anatomical regions of the GI tract. In humans, small intestinal motility recovers within several hours, whereas the recovery of gastric function takes 1 to 2 days, and colonic propulsive motility requires at least 2 to 3 days for recovery (Condon et al., 1986). There are currently no pharmacological agents available to normalize gut motility, and the pharmacologic...

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Section: Discussionsupporting

confidence: 93%

Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus

Venkova¹,

Mann²,

Nelson³

et al. 2009

J Pharmacol Exp Ther

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“…Moreover, we show for the first time that the effect of ghrelin on body weight is agedependent, being most pronounced in the youngest rats. Importantly, although less prominent, the response of older rats to a stimulatory effect of ghrelin on body weight was still significant, which agrees with the ability of peripheral ghrelin to prevent body weight loss in senescent Brown Norway rats (Yukawa et al, 2008). Also, i.c.v.…”

Section: Discussionsupporting

confidence: 76%

Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats

Nešić

Stevanović

Stanković

et al. 2013

European Journal of Pharmacology

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“…The finding of increased adiposity without increased FI supports findings of a previous study indicating that central ghrelin can alter adipocyte metabolism independently of an effect on FI. Other studies have shown that ghrelin stimulates adipogenesis [19], alters energy partitioning into fat [20], and decreases sympathetic activity and metabolic rate [21], also supporting a FI-independent effect of ghrelin on adipose tissue metabolism. In our study, the lack of effect on FI was likely due to the much lower doses that we tested, compared to other studies showing both increased adiposity and increased FI with ICV or peripheral ghrelin treatment (see, for example, [14,22]).…”

Section: Discussionmentioning

confidence: 77%

Central leptin versus ghrelin: effects on bone marrow adiposity and gene expression

Ambati

Rayalam

et al. 2009

Endocr

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This study compared the central effects of ghrelin and leptin on body and bone marrow adiposity and gene expression in adipose tissue and bone marrow. Male Sprague-Dawley rats were injected intracerebroventricular (ICV) twice daily with control, 66 ng ghrelin (G66), 330 ng ghrelin (G330), or 5 μg leptin (L5) for 5 days. Food intake (FI) and body weight (BW) were measured daily. Gene expression in adipose tissue and bone marrow was assessed using RT-PCR. Leptin reduced FI (P < 0.05) and BW (P < 0.05), whereas ghrelin increased BW (P < 0.05) without affecting FI. Leptin decreased fat pad weights, whereas ghrelin (G330) increased fat pad weights (P < 0.05). In epididymal adipose tissue, leptin increased expression of lipolysis marker ADRB2 and thermogenesis marker MFN2 and decreased expression of adipogenic markers, FASN, SLC2A4, and SCD1, whereas ghrelin increased expression of FASN and SCD1. Leptin decreased bone marrow adipocyte size and number; however, ghrelin had no effect on these parameters. In whole bone marrow, leptin decreased expression of FASN and SCD1 and increased expression of DLK1, whereas ghrelin (G330) decreased expression of COL1A1. Thus, leptin induces similar changes in bone marrow and adipose tissue gene expression, reflecting the decreased adiposity in both compartments.

show abstract

Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Abstract: Yukawa M, Weigle DS, Davis CD, Marck BT, Wolden-Hanson T. Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery.

Cited by 14 publications

References 73 publications

Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus

Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus

Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats

Central leptin versus ghrelin: effects on bone marrow adiposity and gene expression

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