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The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake.

Caruso V, Le Grevés M, Shirazi Fard S, Haitina T, Olszewski PK, Alsiö J, Schiöth HB, Fredriksson R - PLoS ONE (2015)

Bottom Line: Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus.Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food.Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University, Uppsala, Sweden.

ABSTRACT
G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12-48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

No MeSH data available.


Related in: MedlinePlus

Gpr178 mRNA expression during food intake experiments.(A) Gpr178 mRNA expression after short-term exposure to starvation in mice; control group, had unlimited access to chow diet; n = 8 each group. (B) Gpr178 mRNA expression after long-term exposure (48 hours) in rat. Control group had unlimited access to chow diet, whereas restricted group was provided with 45% of the total daily caloric intake of the control group. Restricted group had free access to food until 48h before the end point of the experiment. N = 8 each group. (C) Gpr178 mRNA expression in mice after short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose); n = 8 each group. (D) Gpr178 mRNA expression in mice after long-term (10days) exposure to high-fat or high-carbohydrate diet; n = 8. BS, Brainstem; HYP, Hypothalamus; PFC, Prefrontal cortex; AMY, Amygdala. Data were analysed by two-way ANOVA followed by post hoc LSD (A, 12h starvation/24h starvation; B, restricted/48h starvation; C, Intralipid/10% sucrose; D, high-sugar/high-fat or high-carbohydrate diet). * p<0.05 ** p<0.01 ***p<0.001.
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pone.0122061.g003: Gpr178 mRNA expression during food intake experiments.(A) Gpr178 mRNA expression after short-term exposure to starvation in mice; control group, had unlimited access to chow diet; n = 8 each group. (B) Gpr178 mRNA expression after long-term exposure (48 hours) in rat. Control group had unlimited access to chow diet, whereas restricted group was provided with 45% of the total daily caloric intake of the control group. Restricted group had free access to food until 48h before the end point of the experiment. N = 8 each group. (C) Gpr178 mRNA expression in mice after short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose); n = 8 each group. (D) Gpr178 mRNA expression in mice after long-term (10days) exposure to high-fat or high-carbohydrate diet; n = 8. BS, Brainstem; HYP, Hypothalamus; PFC, Prefrontal cortex; AMY, Amygdala. Data were analysed by two-way ANOVA followed by post hoc LSD (A, 12h starvation/24h starvation; B, restricted/48h starvation; C, Intralipid/10% sucrose; D, high-sugar/high-fat or high-carbohydrate diet). * p<0.05 ** p<0.01 ***p<0.001.

Mentions: Gene expression levels of Gpr178 mRNA were measured in tissues isolated from the rat and mouse (Fig 2). In total, 32 and 21 tissues (rat and mouse, respectively) were included in our panels. Overall, Gpr178 mRNA was highly expressed in the rat CNS and the highest expression was detected in cross section V, 11.9 ± 0.8 and cross section VII, 9.3 ± 0.4. Moderate levels of Gpr178 expression were observed in cross section II (5.7 ± 0.2), cross section VI (7.4 ± 0,3), cross section VIII (5.3 ± 0.6), whereas similar levels were found in the brainstem (4.5 ± 0.1), cerebellum (5.6± 0.6), hypothalamus (4.8 ± 0.7), hippocampus (5.5 ± 0.7), eye (4.3 ± 0.4), intestine (6.3 ± 0.3), and olfactory bulb (4.9 ± 0.1). In the mouse, Gpr178 mRNA is highly expressed in the cerebellum (78.3 ± 15.1), lung (56.5 ± 19.2), whereas similar levels were found in the neocortex, striatum, hippocampus, brainstem and substantia nigra. Moderate to low Gpr178 mRNA levels were found in additional tissue types (Fig 2). Several diet paradigms were used to investigate Gpr178 mRNA levels in mice (detailed description in S1 Dataset). In an initial experiment, mice were exposed to both 12 and 24 hours of acute starvation. Our results indicated a significant hypothalamic and brainstem increase after 12 hours of starvation (p<0.05 and p<0.001, respectively). While mRNA transcription levels returned to control levels after 24 hours of starvation in the brainstem, this increase remained significant in the hypothalamus (Fig 3A). In line with these results, rats exposed to food restriction followed by long-term starvation (48 hours) showed significantly higher levels of Gpr178 mRNA in the prefrontal cortex compared to control group (p< 0.01). In the same experiment, Gpr178 mRNA expression remained unchanged in the hypothalamus and amygdala (Fig 3B). We evaluated the relationship between Gpr178 mRNA expression and short- and long-term overconsumption of palatable diets. Mice having short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose) had lower mRNA levels of Gpr178 in the brainstem compared to controls, while their hypothalamic levels remained unchanged (Fig 3C). No change in mRNA levels was observed after long-term (21 days) free access to the sugar solution, similarly to rats exposed to same treatment for 14 days (Data not shown). On the other hand, a decrease in the relative Gpr178 mRNA content was detected in the amygdala of rats fed the high-fat or high-carbohydrate diets (Fig 3D). No differences in expression levels of Gpr178 in the hypothalamus were observed.


The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake.

Caruso V, Le Grevés M, Shirazi Fard S, Haitina T, Olszewski PK, Alsiö J, Schiöth HB, Fredriksson R - PLoS ONE (2015)

Gpr178 mRNA expression during food intake experiments.(A) Gpr178 mRNA expression after short-term exposure to starvation in mice; control group, had unlimited access to chow diet; n = 8 each group. (B) Gpr178 mRNA expression after long-term exposure (48 hours) in rat. Control group had unlimited access to chow diet, whereas restricted group was provided with 45% of the total daily caloric intake of the control group. Restricted group had free access to food until 48h before the end point of the experiment. N = 8 each group. (C) Gpr178 mRNA expression in mice after short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose); n = 8 each group. (D) Gpr178 mRNA expression in mice after long-term (10days) exposure to high-fat or high-carbohydrate diet; n = 8. BS, Brainstem; HYP, Hypothalamus; PFC, Prefrontal cortex; AMY, Amygdala. Data were analysed by two-way ANOVA followed by post hoc LSD (A, 12h starvation/24h starvation; B, restricted/48h starvation; C, Intralipid/10% sucrose; D, high-sugar/high-fat or high-carbohydrate diet). * p<0.05 ** p<0.01 ***p<0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4457792&req=5

pone.0122061.g003: Gpr178 mRNA expression during food intake experiments.(A) Gpr178 mRNA expression after short-term exposure to starvation in mice; control group, had unlimited access to chow diet; n = 8 each group. (B) Gpr178 mRNA expression after long-term exposure (48 hours) in rat. Control group had unlimited access to chow diet, whereas restricted group was provided with 45% of the total daily caloric intake of the control group. Restricted group had free access to food until 48h before the end point of the experiment. N = 8 each group. (C) Gpr178 mRNA expression in mice after short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose); n = 8 each group. (D) Gpr178 mRNA expression in mice after long-term (10days) exposure to high-fat or high-carbohydrate diet; n = 8. BS, Brainstem; HYP, Hypothalamus; PFC, Prefrontal cortex; AMY, Amygdala. Data were analysed by two-way ANOVA followed by post hoc LSD (A, 12h starvation/24h starvation; B, restricted/48h starvation; C, Intralipid/10% sucrose; D, high-sugar/high-fat or high-carbohydrate diet). * p<0.05 ** p<0.01 ***p<0.001.
Mentions: Gene expression levels of Gpr178 mRNA were measured in tissues isolated from the rat and mouse (Fig 2). In total, 32 and 21 tissues (rat and mouse, respectively) were included in our panels. Overall, Gpr178 mRNA was highly expressed in the rat CNS and the highest expression was detected in cross section V, 11.9 ± 0.8 and cross section VII, 9.3 ± 0.4. Moderate levels of Gpr178 expression were observed in cross section II (5.7 ± 0.2), cross section VI (7.4 ± 0,3), cross section VIII (5.3 ± 0.6), whereas similar levels were found in the brainstem (4.5 ± 0.1), cerebellum (5.6± 0.6), hypothalamus (4.8 ± 0.7), hippocampus (5.5 ± 0.7), eye (4.3 ± 0.4), intestine (6.3 ± 0.3), and olfactory bulb (4.9 ± 0.1). In the mouse, Gpr178 mRNA is highly expressed in the cerebellum (78.3 ± 15.1), lung (56.5 ± 19.2), whereas similar levels were found in the neocortex, striatum, hippocampus, brainstem and substantia nigra. Moderate to low Gpr178 mRNA levels were found in additional tissue types (Fig 2). Several diet paradigms were used to investigate Gpr178 mRNA levels in mice (detailed description in S1 Dataset). In an initial experiment, mice were exposed to both 12 and 24 hours of acute starvation. Our results indicated a significant hypothalamic and brainstem increase after 12 hours of starvation (p<0.05 and p<0.001, respectively). While mRNA transcription levels returned to control levels after 24 hours of starvation in the brainstem, this increase remained significant in the hypothalamus (Fig 3A). In line with these results, rats exposed to food restriction followed by long-term starvation (48 hours) showed significantly higher levels of Gpr178 mRNA in the prefrontal cortex compared to control group (p< 0.01). In the same experiment, Gpr178 mRNA expression remained unchanged in the hypothalamus and amygdala (Fig 3B). We evaluated the relationship between Gpr178 mRNA expression and short- and long-term overconsumption of palatable diets. Mice having short-term (48 hours) full access to palatable drinking solutions (4.1% Intralipid or 10% sucrose) had lower mRNA levels of Gpr178 in the brainstem compared to controls, while their hypothalamic levels remained unchanged (Fig 3C). No change in mRNA levels was observed after long-term (21 days) free access to the sugar solution, similarly to rats exposed to same treatment for 14 days (Data not shown). On the other hand, a decrease in the relative Gpr178 mRNA content was detected in the amygdala of rats fed the high-fat or high-carbohydrate diets (Fig 3D). No differences in expression levels of Gpr178 in the hypothalamus were observed.

Bottom Line: Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus.Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food.Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Unit of Functional Pharmacology, Uppsala University, Uppsala, Sweden.

ABSTRACT
G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12-48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

No MeSH data available.


Related in: MedlinePlus