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. 2019 Dec;8(1):1-15.
doi: 10.1080/21623945.2018.1528811. Epub 2018 Oct 9.

Acylated and unacylated ghrelin directly regulate ß-3 stimulated lipid turnover in rodent subcutaneous and visceral adipose tissue ex vivo but not in vivo

Daniel T Cervone  1 , Justin Sheremeta  1 , Emily N Kraft  1 , David J Dyck  1
Affiliations

Acylated and unacylated ghrelin directly regulate ß-3 stimulated lipid turnover in rodent subcutaneous and visceral adipose tissue ex vivo but not in vivo

Daniel T Cervone et al. Adipocyte. 2019 Dec.

Abstract

Ghrelin has garnered interest as a gut-derived regulator of lipid metabolism, beyond its classical roles in driving appetite and growth hormone release. Ghrelin's circulating concentrations follow an ultradian rhythm, peak immediately before a meal and point towards a potential metabolic role in reducing the mobilization of fatty acid stores in preparation for the storage of ingested food. Here, we demonstrate that both acylated and unacylated ghrelin have physiological roles in attenuating lipolysis in mature subcutaneous and visceral adipose tissue depots of rats. Ghrelin blunted the ß3-induction (CL 316, 243) of glycerol release (index of lipolysis) which coincided with a reduced activation of the key lipid hydrolase HSL at two of its serine residues (Ser563/660). Furthermore, ghrelin appeared to inhibit fatty acid reesterification in the presence of CL such that fatty acid concentrations in the surrounding media were maintained in spite of a reduction in lipolysis. Importantly, these aforementioned effects were not observed following ghrelin injection in vivo, as there was no attenuation of CL-induced glycerol release. This highlights the importance of exercising caution when interpreting the effects of administering ghrelin in vivo, and the necessity for uncovering the elusive mechanisms by which ghrelin regulates lipolysis and fatty acid reesterification. We conclude that both acylated and unacylated ghrelin can exert direct inhibitory effects on lipolysis and fatty acid reesterification in adipose tissue from rats. However, these effects are not observed in vivo and outline the complexity of studying ghrelin's effects on fatty acid metabolism in the living animal.

Keywords: adrenergic; endocrinology; fatty acids; growth hormone; lipolysis; metabolism; orexigenic; organ culture; reesterification; signaling.

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Figures

Figure 1.
Figure 1.
The ex vivo effects of CL and CL + ghrelin combination treatments on lipolysis as measured by glycerol (a and d) and free fatty acid (b and e) release and fatty acid reesterification (c and f) in subcutaneous inguinal white (top) and visceral retroperitoneal (bottom) adipose tissue. Data were analyzed using a repeated measures two-way ANOVA (n = 9–12) and expressed as mean ± standard error, in mM/g tissue/2h. Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 2.
Figure 2.
The ex vivo effects of GH and GH + ghrelin or CL combination treatments on lipolysis as measured by glycerol (a and d) and free fatty acid (b and e) release and fatty acid reesterification (c and f) in subcutaneous inguinal white (top) and visceral retroperitoneal (bottom) adipose tissue. Data were analyzed using a repeated measures one-way ANOVA (n = 6–8) and expressed as mean ± standard error, in mM/g tissue/2h. Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 3.
Figure 3.
The ex vivo effects of CL and CL + ghrelin combination treatments on the activation of lipolytic enzymes ATGL and HSL in subcutaneous inguinal white (a) and visceral retroperitoneal (b) adipose tissue. Data were analyzed using a repeated measures one-way ANOVA (n = 6–12) and expressed as mean ± standard error, in arbitrary protein units (phospho/total). Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 4.
Figure 4.
The ex vivo effects of CL and CL + ghrelin combination treatments on the activation of ERK, the cellular energy-sensing enzyme AMPK and its downstream target ACC in subcutaneous inguinal white (a) and visceral retroperitoneal (b) adipose tissue. Data were analyzed using a repeated measures one-way ANOVA (n = 8–10) and expressed as mean ± standard error, in arbitrary protein units (phospho/total). Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 5.
Figure 5.
The in vivo effects of CL and CL + ghrelin co-injections on lipolysis as measured by circulating glycerol (a) and free fatty acid (b) release and fatty acid reesterification (c). Data were analyzed using a repeated measures one-way ANOVA (n = 7–8) and expressed as mean ± standard error, in mM. Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 6.
Figure 6.
The in vivo effects of CL and CL + ghrelin co-injections on the activation of lipolytic enzymes ATGL and HSL in subcutaneous inguinal white (a) and visceral retroperitoneal (b) adipose tissue. Data were analyzed using a repeated measures one-way ANOVA (n = 6–8) and expressed as mean ± standard error, in arbitrary protein units (phospho/total). Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
Figure 7.
Figure 7.
The in vivo effects of CL and CL + ghrelin co-injections on the activation of ERK, the cellular energy-sensing enzyme AMPK and its downstream target ACC in subcutaneous inguinal white (a) and visceral retroperitoneal (b) adipose tissue. Data were analyzed using a repeated measures one-way ANOVA (n = 6–8) and expressed as mean ± standard error, in arbitrary protein units (phospho/total). Data sharing a letter are not statistically different from each other. p < 0.05 was considered statistically significant.
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References

    1. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA, et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes. 2001;50:2540–2547. - PubMed
    1. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DGA, Ghatei MA, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325–4328. - PubMed
    1. Liu J, Prudom CE, Nass R, Pezzoli SS, Oliveri MC, Johnson ML, Veldhuis P, Gordon DA, Howard AD, Witcher DR, et al. Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. J Clin Endocrinol Metab. 2008;93:1980–1987. - PMC - PubMed
    1. Barazzoni R, Bosutti A, Stebel M, Cattin MR, Roder E, Visintin L, Cattin L, Biolo G, Zanetti M, Guarnieri G.. Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am J Physiol Endocrinol Metab. 2005;288:228–235. - PubMed
    1. Vestergaard ET, Djurhuus CB, Gjedsted J, Nielsen S, Møller N, Holst JJ, Jørgensen JOL, Schmitz O. Acute effects of ghrelin administration on glucose and lipid metabolism. J Clin Endocrinol Metab. 2008;93:438–444. - PubMed

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