36 research outputs found
Increased body weight/adiposity despite reduced food intake in Y1Y5<sup>β/β</sup> mice on chow.
<p>(AβH) Spontaneous (A, C, E, G) and accumulated (accum) 24-hour fasting-induced food intake (B, D, F, H), normalised to body weight, in male and female germline Y1Y5 receptor knockout (Y1Y5<sup>β/β</sup>) and wildtype control (WT) mice at 18 and 34 weeks of age. (IβJ) Body weight from 16 to 36 weeks of age in male (I) and female (J) Y1Y5<sup>β/β</sup> or WT mice. (KβP) Fat and lean masses as a percentage of body weight (%BW), measured using dual energy x-ray absorptiometry, in male (K, O) and female (M, P) Y1Y5<sup>β/β</sup> and WT mice at 20 and 36 weeks of age. Weight (as %BW) of dissected white (WAT) and brown adipose tissue (BAT) depots at the end of the study in male (L) and female (N) Y1Y5<sup>β/β</sup> and WT mice at 36 weeks of age. Abbreviations: i, inguinal; g, gonadal; m, mesenteric; r, retroperitoneal; total, summed weight of i, g, m and r WAT depots. Plotted values are means Β± SEM of 5β12 standard chow-fed mice per group. *P<0.05, **P<0.01 or ***P<0.001 for Y1Y5<sup>β/β</sup> versus WT mice of the same age and sex.</p
Reduced ARC NPY expression and increased body weight in young Y1Y5<sup>β/β</sup> mice on chow.
<p>(AβB) Bright field photomicrographs of coronal brain sections from 15 week old male wildtype control (WT, A) and germline Y1Y5 receptor knockout (Y1Y5<sup>β/β</sup>, B) mice after <i>in situ</i> hybridisation for NPY mRNA. Scale bar β=β25 Β΅m. Abbreviations: 3V; third ventricle, ARC, arcuate nucleus of the hypothalamus. (CβD) Body weight from 5 to 15 weeks of age in male (C) and 5 to 13 weeks of age in female (D) WT or Y1Y5<sup>β/β</sup> mice. Plotted values are means Β± SEM of 4β21 standard chow-fed mice per group. ***P<0.001 for Y1Y5<sup>β/β</sup> versus WT mice of the same age and sex.</p
Peptide YY Regulates Bone Remodeling in Mice: A Link between Gut and Skeletal Biology
<div><h3>Background & Aims</h3><p>Gastrointestinal peptides are increasingly being linked to processes controlling the maintenance of bone mass. Peptide YY (PYY), a gut-derived satiety peptide of the neuropeptide Y family, is upregulated in some states that also display low bone mass. Importantly, PYY has high affinity for Y-receptors, particularly Y1R and Y2R, which are known to regulate bone mass. Anorexic conditions and bariatric surgery for obesity influence circulating levels of PYY and have a negative impact on bone mass, but the precise mechanism behind this is unclear. We thus examined whether alterations in PYY expression affect bone mass.</p> <h3>Methods</h3><p>Bone microstructure and cellular activity were analyzed in germline PYY knockout and conditional adult-onset PYY over-expressing mice at lumbar and femoral sites using histomorphometry and micro-computed tomography.</p> <h3>Results</h3><p>PYY displayed a negative relationship with osteoblast activity. Male and female PYY knockout mice showed enhanced osteoblast activity, with greater cancellous bone mass. Conversely, PYY over-expression lowered osteoblast activity <em>in vivo</em>, via a direct Y1 receptor mediated mechanism involving MAPK stimulation evident <em>in vitro</em>. In contrast to PYY knockout mice, PYY over expression also altered bone resorption, as indicated by greater osteoclast surface, despite the lack of Y-receptor expression in osteoclastic cells. While evident in both sexes, cellular changes were generally more pronounced in females.</p> <h3>Conclusions</h3><p>These data demonstrate that the gut peptide PYY is critical for the control of bone remodeling. This regulatory axis from the intestine to bone has the potential to contribute to the marked bone loss observed in situations of extreme weight loss and higher circulating PYY levels, such as anorexia and bariatric obesity surgery, and may be important in the maintenance of bone mass in the general population.</p> </div
Altered energy expenditure and decreased respiratory exchange ratio in Y1Y5<sup>β/β</sup> mice on chow.
<p>(AβL) 24-hour time course of energy expenditure (AβD), physical activity (EβH) and respiratory exchange ratio (IβL) in male and female germline Y1Y5 receptor knockout (Y1Y5<sup>β/β</sup>) or wildtype control (WT) mice at 20 and 36 weeks of age. Energy expenditure was adjusted for lean mass by analysis of covariance (ANCOVA). Adjusted energy expenditure was presented at a common lean mass of 21.936 g (males) and 16.015 g (females) at 20 weeks of age and 23.172 g (males) and 17.115 g (females) at 36 weeks of age. Open and filled horizontal bars indicate light and dark phases, respectively. Plotted values are means Β± SEM of 5β12 standard chow-fed mice per group. *P<0.05, **P<0.01, or ***P<0.001 for Y1Y5<sup>β/β</sup> versus WT mice of the same age and sex.</p
Unaltered energy expenditure and decreased physical activity in chow-fed mice with adult-onset hypothalamus-specific Y1Y5 receptor deletion.
<p>(AβL) 24-hour time course of energy expenditure (AβD), physical activity (EβH) and respiratory exchange ratio (IβL) in male and female adult-onset hypothalamus-specific Y1Y5 receptor knockout (Y1Y5<sup>Hyp/Hyp</sup>) or control (Y1Y5<sup>lox/lox</sup>) mice at 19 and 36 weeks of age. Energy expenditure was adjusted for lean mass by analysis of covariance (ANCOVA). Adjusted energy expenditure was presented at a common lean mass of 21.629 g (males) and 16.252 g (females) at 19 weeks of age and 22.762 g (males) and 18.865 g (females) at 36 weeks of age. Open and filled horizontal bars indicate light and dark phases, respectively. Plotted values are means Β± SEM of 5β12 standard chow-fed mice per group. *P<0.05 or **P<0.01 for Y1Y5<sup>Hyp/Hyp</sup> versus Y1Y5<sup>lox/lox</sup> mice of the same age and sex.</p
Altered blood glucose responses to glucose and insulin after adult-onset hypothalamus-specific Y1Y5 receptor deletion.
<p>(AβH) Intraperitoneal glucose tolerance tests (1 g/kg) were conducted in 24-hour fasted male (A, B, E, F) and female (C, D, G, H) adult-onset hypothalamus-specific Y1Y5 receptor deficient (Y1Y5<sup>Hyp/Hyp</sup>) or control (Y1Y5<sup>lox/lox</sup>) mice at 18 or 35 weeks of age. (IβP). Intraperitoneal insulin tolerance tests (0.5 U/kg) were conducted in 6-hour fasted male (I, J, M, N) and female (K, L, O, P) Y1Y5<sup>Hyp/Hyp</sup> or control Y1Y5<sup>lox/lox</sup> mice at 18 or 35 weeks of age. Plotted values are means Β± SEM of 5β12 chow or high fat diet (HFD)-fed mice per group. *P<0.05 or **P<0.01 for Y1Y5<sup>Hyp/Hyp</sup> versus Y1Y5<sup>lox/lox</sup> mice of the same age, sex and diet.</p
Effect of adult-onset hypothalamus-specific Y1Y5 receptor deletion on weight regain after a 24-hour fast.
<p>Body weight measurements were taken at the time points of fasting-induced food intake measurements in male (A, C, E, G) and female (B, D, F, H) adult-onset hypothalamus-specific Y1Y5 receptor knockout (Y1Y5<sup>Hyp/Hyp</sup>) or control (Y1Y5<sup>lox/lox</sup>) mice, at both 17 and 34 weeks of age and on a standard chow (Chow) or a high fat diet (HFD). Data are represented as a percent of pre-fasting body weight (%basal). Absolute pre-fasting body weights at 17 weeks of age were Y1Y5<sup>lox/lox</sup> male β=β25.4Β±0.6 g (standard chow), 28.0Β±0.6 g (HFD); Y1Y5<sup>β/β</sup> male β=β26.1Β±0.9 g (standard chow), 28.9Β±0.9 g (HFD); Y1Y5<sup>lox/lox</sup> female β=β20.1Β±0.5 g (standard chow), 21.6Β±1.0 g (HFD); Y1Y5<sup>β/β</sup> female β=β20.1Β±0.6 g (standard chow), 21.6Β±0.8 g (HFD), and at 34 weeks of age were Y1Y5<sup>lox/lox</sup> male β=β30.0Β±1.3 g (standard chow), 34.0Β±1.5 g (HFD); Y1Y5<sup>β/β</sup> male β=β31.2Β±1.6 g (standard chow), 40.2Β±1.6 g (HFD); Y1Y5<sup>lox/lox</sup> female β=β24.7Β±0.7 g (standard chow), 27.9Β±1.5 g (HFD); Y1Y5<sup>β/β</sup> female β=β27.1Β±2.0 g (standard chow), 29.9Β±1.3 g (HFD). Plotted values are means Β± SEM of 4β21 mice per group. *P<0.05 for Y1Y5<sup>Hyp/Hyp</sup> versus Y1Y5<sup>lox/lox</sup> mice of the same age, sex and diet.</p
No effect of adult-onset hypothalamus-specific Y1Y5 receptor deletion on energy homeostasis on a chow diet.
<p>(AβH) Spontaneous (A, C, E, G) and accumulated (accum) 24-hour fasting-induced food intake (B, D, F, H), normalised to body weight, in adult-onset hypothalamus-specific Y1Y5 receptor deficient (Y1Y5<sup>Hyp/Hyp</sup>) or control (Y1Y5<sup>lox/lox</sup>) mice at 18 and 34 weeks of age. (IβJ) Body weight from 12 to 36 weeks of age in male (I) and female (J) Y1Y5<sup>Hyp/Hyp</sup> or Y1Y5<sup>lox/lox</sup> control mice. βPVN injectionβ refers to the time of induction of gene deletion by injection of a Cre-recombinase-expressing viral vector into the paraventricular nucleus of the hypothalamus. (KβP) Fat and lean masses as a percentage of body weight (%BW), measured using dual energy x-ray absorptiometry, in male (K, O) and female (M, P) Y1Y5<sup>Hyp/Hyp</sup> and Y1Y5<sup>lox/lox</sup> mice at 19, 27 and 36 weeks of age. Weight (as %BW) of dissected white (WAT) and brown adipose tissue (BAT) depots at the end of the study in male (L) and female (N) Y1Y5<sup>Hyp/Hyp</sup> and Y1Y5<sup>lox/lox</sup> mice at 36 weeks of age. Abbreviations: i, inguinal; g, gonadal; m, mesenteric; r, retroperitoneal; total, summed weight of i, g, m and r WAT depots. Plotted values are means Β± SEM of 5β12 standard chow-fed mice per group.</p
Obesity despite hypophagia after adult-onset hypothalamus-specific Y1Y5 deletion in mice on a high fat diet.
<p>(AβH) Spontaneous (A, C, E, G) and accumulated (accum) 24-hour fasting-induced food intake (B, D, F, H), normalised to body weight, in adult-onset hypothalamus-specific Y1Y5 receptor deficient (Y1Y5<sup>Hyp/Hyp</sup>) or control (Y1Y5<sup>lox/lox</sup>) mice at 18 and 34 weeks of age. (IβJ) Body weight from 12 to 36 weeks of age in male (I) and female Y1Y5<sup>Hyp/Hyp</sup> or Y1Y5<sup>lox/lox</sup> mice. Mice were on the high fat diet (HFD) from 16 weeks of age onwards. βPVN injectionβ refers to the time of induction of gene deletion by injection of a Cre-recombinase-expressing viral vector into the paraventricular nucleus of the hypothalamus. (KβP) Fat and lean masses as a percentage of body weight (%BW), measured using dual energy x-ray absorptiometry, in male (K, O) and female (M, P) Y1Y5<sup>Hyp/Hyp</sup> and Y1Y5<sup>lox/lox</sup> mice at 19, 27 and 36 weeks of age. Weight (as %BW) of dissected white (WAT) and brown adipose tissue (BAT) depots at the end of the study in male (L) and female (N) Y1Y5<sup>Hyp/Hyp</sup> and Y1Y5<sup>lox/lox</sup> mice at 36 weeks of age. Abbreviations: i, inguinal; g, gonadal; m, mesenteric; r, retroperitoneal; total, summed weight of i, g, m and r WAT depots. Plotted values are means Β± SEM of 5β12 HFD-fed mice per group. *P<0.05 or **P<0.01 for Y1Y5<sup>Hyp/Hyp</sup> versus Y1Y5<sup>lox/lox</sup> mice of the same age and sex.</p
Slower weight regain after a 24-hour fast in Y1Y5<sup>β/β</sup> mice on chow.
<p>Body weight measurements were taken at the time points of fasting-induced food intake measurements in male (A, C) and female (B, D) germline Y1Y5 receptor knockout (Y1Y5<sup>β/β</sup>) or wildtype control (WT) mice, at both 18 and 34 weeks of age. Data are presented as a percent of pre-fasting body weight (%basal). Absolute pre-fasting body weights at 18 weeks of age were WT male β=β25.4Β±0.6 g; Y1Y5<sup>β/β</sup> male β=β29.3Β±1.8 g; WT female β=β19.7Β±0.5 g; Y1Y5<sup>β/β</sup> female β=β20.1Β±0.4 g, and at 34 weeks of age, WT male β=β30.1Β±1.3 g; Y1Y5<sup>β/β</sup> male β=β35.5Β±1.2 g; WT female β=β24.5Β±0.7 g; Y1Y5<sup>β/β</sup> female β=β25.0Β±0.9 g. Plotted values are means Β± SEM of 4β21 standard chow-fed mice per group. **P<0.01 or ***P<0.001 for Y1Y5<sup>β/β</sup> versus WT mice of the same age and sex.</p