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Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass.

Uchida A, Zechner JF, Mani BK, Park WM, Aguirre V, Zigman JM - Mol Metab (2014)

Bottom Line: We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB.In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion - glucose and norepinephrine.In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT
The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghrelin cell responsiveness to physiological cues. We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB. In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion - glucose and norepinephrine. In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed. Our findings provide new insights into the regulation of ghrelin secretion and its relation to circulating ghrelin within the contexts of obesity and weight loss.

No MeSH data available.


Related in: MedlinePlus

Elevated fasting plasma ghrelin levels in RYGB mice. (A) Study time line for ALS, WMS and RYGB mice. (B) Body weights were reduced post-operatively in RYGB compared to ALS mice. Body weights of WMS were maintained similar to RYGB mice through restricted caloric intake and are lower compared to ALS mice (n = 16–20 mice). Asterisk for this figure denotes difference compared to ALS mice for both RYGB and WMS mice at each time point. (C) Daily food intake measured over 5 consecutive days was similar in RYGB and ALS mice at 5 weeks post-surgery. Food measurements shown for the WMS mice are calorie requirements to match the body weight of RYGB mice (n = 8–15 mice). (D) Body composition measurements at 5 weeks post-surgery show reduction in fat mass in RYGB and WMS compared to ALS mice, but no change in lean mass (n = 16–17 mice). (E) Fasting blood glucose (left, n = 16–20 mice) and fasting insulin levels (right, n = 8 mice) were improved in RYGB and WMS mice compared to ALS mice. (F) Fasting acyl-ghrelin levels (right, n = 15–16 mice) were elevated in RYGB compared to WMS and ALS mice. Fasting desacyl-ghrelin levels (right, n = 11–15 mice) were different among RYGB, WMS and ALS mice. Data are represented as mean ± SEM. *P < 0.05 compared to ALS mice, #P < 0.05 compared to RYGB mice and §P < 0.05 compared to WMS mice.
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fig3: Elevated fasting plasma ghrelin levels in RYGB mice. (A) Study time line for ALS, WMS and RYGB mice. (B) Body weights were reduced post-operatively in RYGB compared to ALS mice. Body weights of WMS were maintained similar to RYGB mice through restricted caloric intake and are lower compared to ALS mice (n = 16–20 mice). Asterisk for this figure denotes difference compared to ALS mice for both RYGB and WMS mice at each time point. (C) Daily food intake measured over 5 consecutive days was similar in RYGB and ALS mice at 5 weeks post-surgery. Food measurements shown for the WMS mice are calorie requirements to match the body weight of RYGB mice (n = 8–15 mice). (D) Body composition measurements at 5 weeks post-surgery show reduction in fat mass in RYGB and WMS compared to ALS mice, but no change in lean mass (n = 16–17 mice). (E) Fasting blood glucose (left, n = 16–20 mice) and fasting insulin levels (right, n = 8 mice) were improved in RYGB and WMS mice compared to ALS mice. (F) Fasting acyl-ghrelin levels (right, n = 15–16 mice) were elevated in RYGB compared to WMS and ALS mice. Fasting desacyl-ghrelin levels (right, n = 11–15 mice) were different among RYGB, WMS and ALS mice. Data are represented as mean ± SEM. *P < 0.05 compared to ALS mice, #P < 0.05 compared to RYGB mice and §P < 0.05 compared to WMS mice.

Mentions: Male C57BL/6 mice were started on HFD between 4 and 5 weeks of age. After 12–15 weeks of HFD feeding, mice (approximately 45 g in body weight) were randomized to either RYGB- or sham-operated groups. Mice were allowed to recover under previously described post-operative care [79] during which a liquid diet (Vital HN; Abbott Laboratories, Abbott Park, IL) was provided on post-surgery days 2 through 7. On post-surgery days 6 and 7, 0.25 g HFD was reintroduced and on post-surgery day 8, HFD was provided ad libitum. Seven days post-surgery, a subset of sham-operated mice was calorically restricted and weight matched to RYGB counterparts (weight-matched sham; WMS). All RYGB-operated and the remaining sham-operated mice (ad libitum sham; ALS) were provided HFD ad libitum starting post-surgery day 8. All mice were weighed at 7, 11, 14, 21, 28 and 35 days post-surgery (Figure 3A). At 5 weeks post-surgery, food intake was measured on 5 consecutive days and body composition was evaluated using a Minispec mq10 nuclear magnetic resonance analyzer (NMR; Bruker Optics, Billerica, MA). At 6 weeks post-surgery, the mice were either perfused and formalin fixed for immunohistochemistry or euthanized for isolation of gastric mucosal cells to establish primary cultures. All mice in these studies were euthanized after an overnight fast (6 PM–10 AM).


Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass.

Uchida A, Zechner JF, Mani BK, Park WM, Aguirre V, Zigman JM - Mol Metab (2014)

Elevated fasting plasma ghrelin levels in RYGB mice. (A) Study time line for ALS, WMS and RYGB mice. (B) Body weights were reduced post-operatively in RYGB compared to ALS mice. Body weights of WMS were maintained similar to RYGB mice through restricted caloric intake and are lower compared to ALS mice (n = 16–20 mice). Asterisk for this figure denotes difference compared to ALS mice for both RYGB and WMS mice at each time point. (C) Daily food intake measured over 5 consecutive days was similar in RYGB and ALS mice at 5 weeks post-surgery. Food measurements shown for the WMS mice are calorie requirements to match the body weight of RYGB mice (n = 8–15 mice). (D) Body composition measurements at 5 weeks post-surgery show reduction in fat mass in RYGB and WMS compared to ALS mice, but no change in lean mass (n = 16–17 mice). (E) Fasting blood glucose (left, n = 16–20 mice) and fasting insulin levels (right, n = 8 mice) were improved in RYGB and WMS mice compared to ALS mice. (F) Fasting acyl-ghrelin levels (right, n = 15–16 mice) were elevated in RYGB compared to WMS and ALS mice. Fasting desacyl-ghrelin levels (right, n = 11–15 mice) were different among RYGB, WMS and ALS mice. Data are represented as mean ± SEM. *P < 0.05 compared to ALS mice, #P < 0.05 compared to RYGB mice and §P < 0.05 compared to WMS mice.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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fig3: Elevated fasting plasma ghrelin levels in RYGB mice. (A) Study time line for ALS, WMS and RYGB mice. (B) Body weights were reduced post-operatively in RYGB compared to ALS mice. Body weights of WMS were maintained similar to RYGB mice through restricted caloric intake and are lower compared to ALS mice (n = 16–20 mice). Asterisk for this figure denotes difference compared to ALS mice for both RYGB and WMS mice at each time point. (C) Daily food intake measured over 5 consecutive days was similar in RYGB and ALS mice at 5 weeks post-surgery. Food measurements shown for the WMS mice are calorie requirements to match the body weight of RYGB mice (n = 8–15 mice). (D) Body composition measurements at 5 weeks post-surgery show reduction in fat mass in RYGB and WMS compared to ALS mice, but no change in lean mass (n = 16–17 mice). (E) Fasting blood glucose (left, n = 16–20 mice) and fasting insulin levels (right, n = 8 mice) were improved in RYGB and WMS mice compared to ALS mice. (F) Fasting acyl-ghrelin levels (right, n = 15–16 mice) were elevated in RYGB compared to WMS and ALS mice. Fasting desacyl-ghrelin levels (right, n = 11–15 mice) were different among RYGB, WMS and ALS mice. Data are represented as mean ± SEM. *P < 0.05 compared to ALS mice, #P < 0.05 compared to RYGB mice and §P < 0.05 compared to WMS mice.
Mentions: Male C57BL/6 mice were started on HFD between 4 and 5 weeks of age. After 12–15 weeks of HFD feeding, mice (approximately 45 g in body weight) were randomized to either RYGB- or sham-operated groups. Mice were allowed to recover under previously described post-operative care [79] during which a liquid diet (Vital HN; Abbott Laboratories, Abbott Park, IL) was provided on post-surgery days 2 through 7. On post-surgery days 6 and 7, 0.25 g HFD was reintroduced and on post-surgery day 8, HFD was provided ad libitum. Seven days post-surgery, a subset of sham-operated mice was calorically restricted and weight matched to RYGB counterparts (weight-matched sham; WMS). All RYGB-operated and the remaining sham-operated mice (ad libitum sham; ALS) were provided HFD ad libitum starting post-surgery day 8. All mice were weighed at 7, 11, 14, 21, 28 and 35 days post-surgery (Figure 3A). At 5 weeks post-surgery, food intake was measured on 5 consecutive days and body composition was evaluated using a Minispec mq10 nuclear magnetic resonance analyzer (NMR; Bruker Optics, Billerica, MA). At 6 weeks post-surgery, the mice were either perfused and formalin fixed for immunohistochemistry or euthanized for isolation of gastric mucosal cells to establish primary cultures. All mice in these studies were euthanized after an overnight fast (6 PM–10 AM).

Bottom Line: We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB.In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion - glucose and norepinephrine.In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT
The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghrelin cell responsiveness to physiological cues. We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB. In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion - glucose and norepinephrine. In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed. Our findings provide new insights into the regulation of ghrelin secretion and its relation to circulating ghrelin within the contexts of obesity and weight loss.

No MeSH data available.


Related in: MedlinePlus