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The hunting of the snark. Interpretive issues in neurobiological analysis of food-entrained circadian rhythms
664
Abstracts / Appetite 54 (2010) 631–683
Proestrus rats have reduced inflammation and ER stress in the liver after 72 h on a high fat diet C.N. MILLER 1,∗ , D.J. CLEGG 2 , P.T. COONEY 1 , L.M. BROWN 1 1 Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC, USA 2 University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas, TX, USA There is evidence that obesity is characterized by chronic activation of inflammatory pathways. The protective effects of ovarian hormones may be a result of the anti-inflammatory effects of estradiol and progesterone in the muscle and adipose tissue. In the present study we sought to determine if this effect is present when a high-fat (HF) diet is first introduced. Age-matched male and female Long-Evans rats (3-month-old) were given a HF or a low-fat (LF) diet for 72 h (n = 89). Females were phased daily and started on the HF diet on the day of estrus so that 72 h later they would be in proestrus at sacrifice. The liver was extracted and processed using quantitative PCR of IL-6, SOCS3, TNF␣ , and XBP1. Females on the HF diet had lower SOCS3 and TNF␣ expression than their LF controls. However, in males there was no difference in inflammatory gene expression between diet groups. Endoplasmic reticulum (ER) stress, measured by higher expression of XBP1, was reduced in females on the HF diet compared the LF controls. However a sex difference in ER stress did exist. Males in both diet groups had higher XBP1 expression than their female counterparts. These data provide support for the protective role of ovarian hormones in inflammatory diseases. doi:10.1016/j.appet.2010.04.140
Sex differences in diet-induced obesity and central leptin sensitivity in middle-aged rats C.N. MILLER 1,∗ , D.J. CLEGG 2 , P.T. COONEY 1 , L.M. BROWN 1 1 Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC, USA 2 University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas, TX, USA As humans and animals age, many get fatter and develop insulin and leptin resistance, making them more susceptible to the metabolic syndrome. In the current study we sought to determine whether the sex differences in central leptin sensitivity found in young rats disappears with age and if age increases susceptibility to diet-induced obesity. Middle-aged male and female rats (8–9 months old) were maintained on either a low-fat (LF) diet or highfat (HF) diet for 5 weeks and given weekly intra-third-cerebral ventricle (i3vt) injections of leptin (1.5, 3.5, 5.0 and 7.5 g). Females on the LF diet given i3vt leptin had a dose-dependent decrease in FI and BW. In contrast, males on the LF diet were leptin resistant. Females on the HF diet responded to leptin at a higher dose, starting at 5.0 g, while males on the HF diet were leptin resistant. These data indicate that a sex difference in central leptin remains in middle-aged rats, however since age-matched males were significantly heavier than the females, it remains to be determined whether the higher BW played a role. During the study females given the HF diet gained 20% in BW compared to their LF diet controls, while males on the HF diet gained 10% in BW compared to their LF diet controls. These results suggest that aged rats of both sexes are susceptible to diet-induced obesity and that middle-aged female rats remain sensitive to central leptin. doi:10.1016/j.appet.2010.04.141
The hunting of the snark. Interpretive issues in neurobiological analysis of food-entrained circadian rhythms R.E. MISTLBERGER Simon Fraser University, Burnaby, BC, Canada When food is freely available, feeding behavior in mammals is controlled by a circadian clock (the suprachiasmatic nucleus) entrained by daily light–dark cycles. When food is temporally restricted, food seeking behavior comes under control of a separate circadian mechanism entrained to mealtime. The physical location, inputs, outputs and molecular basis of this food-entrainable mechanism have proven difficult to establish and remain contentious, but as this symposium will show, progress has been made. I will discuss interpretive issues in evaluating the effects of lesions and gene manipulations on food-entrained rhythms in rats and mice, with a special focus on the role of the dorsomedial hypothalamus and known circadian clock genes. doi:10.1016/j.appet.2010.04.142
Butorphanol effects on feeding and neuropeptide Y gene expression in the rat A. MITRA 1,∗ , B.A. GOSNELL 1 , C.M. KOTZ 2 , E.M. KIM 2 , M.K. GRACE 2 , C.J. BILLINGTON 2 , A.S. LEVINE 1 1 Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA 2 Veterans Affairs Medical Center, Minneapolis, MN, USA, 3 Minn. Obesity Center, University of Minnesota, St. Paul, MN, USA Butorphanol ([BT] an opioid receptor agonist) is different from other opioid agonists in that a single dose of BT can elicit up to 12 g of chow intake in a satiated rat whereas most opioid agonists induce a mild feeding response (2–3 g). Here, we first examined whether the effectiveness of BT to elicit feeding was affected by dose, time of day, and method of infusion and possible tachyphylaxis following administration. Secondly, we examined whether BT administration influenced hypothalamic NPY gene expression and peptide levels. A single dose administration of BT (4 or 16 mg/kg) significantly increased food intake at 2, 4 and 6 h after administration. However following repeated injections of BT at 4 mg/kg, the cumulative long-term intake of BT-treated rats did not differ from that of controls, indicating that the animals compensate for the increased feeding following BT injection by decreased feeding at a later time. An ascending dose schedule of repeated BT injections resulted in additional feeding. NPY gene expression in the ARC was influenced by feeding status but not by BT. The amount of food consumed and the level of NPY mRNA were inversely correlated. This is consistent with NPYs role in normal feeding. We conclude that the feeding produced by BT is sensitive to dose and dosing paradigm. Further, its mechanism of action does not appear to be mediated by NPY pathways. This work was supported by the VAMC, NIH DK42698, NIDA DA03999 and NIDCR T32DE007288. doi:10.1016/j.appet.2010.04.143
Abstracts / Appetite 54 (2010) 631–683
Proestrus rats have reduced inflammation and ER stress in the liver after 72 h on a high fat diet C.N. MILLER 1,∗ , D.J. CLEGG 2 , P.T. COONEY 1 , L.M. BROWN 1 1 Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC, USA 2 University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas, TX, USA There is evidence that obesity is characterized by chronic activation of inflammatory pathways. The protective effects of ovarian hormones may be a result of the anti-inflammatory effects of estradiol and progesterone in the muscle and adipose tissue. In the present study we sought to determine if this effect is present when a high-fat (HF) diet is first introduced. Age-matched male and female Long-Evans rats (3-month-old) were given a HF or a low-fat (LF) diet for 72 h (n = 89). Females were phased daily and started on the HF diet on the day of estrus so that 72 h later they would be in proestrus at sacrifice. The liver was extracted and processed using quantitative PCR of IL-6, SOCS3, TNF␣ , and XBP1. Females on the HF diet had lower SOCS3 and TNF␣ expression than their LF controls. However, in males there was no difference in inflammatory gene expression between diet groups. Endoplasmic reticulum (ER) stress, measured by higher expression of XBP1, was reduced in females on the HF diet compared the LF controls. However a sex difference in ER stress did exist. Males in both diet groups had higher XBP1 expression than their female counterparts. These data provide support for the protective role of ovarian hormones in inflammatory diseases. doi:10.1016/j.appet.2010.04.140
Sex differences in diet-induced obesity and central leptin sensitivity in middle-aged rats C.N. MILLER 1,∗ , D.J. CLEGG 2 , P.T. COONEY 1 , L.M. BROWN 1 1 Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC, USA 2 University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas, TX, USA As humans and animals age, many get fatter and develop insulin and leptin resistance, making them more susceptible to the metabolic syndrome. In the current study we sought to determine whether the sex differences in central leptin sensitivity found in young rats disappears with age and if age increases susceptibility to diet-induced obesity. Middle-aged male and female rats (8–9 months old) were maintained on either a low-fat (LF) diet or highfat (HF) diet for 5 weeks and given weekly intra-third-cerebral ventricle (i3vt) injections of leptin (1.5, 3.5, 5.0 and 7.5 g). Females on the LF diet given i3vt leptin had a dose-dependent decrease in FI and BW. In contrast, males on the LF diet were leptin resistant. Females on the HF diet responded to leptin at a higher dose, starting at 5.0 g, while males on the HF diet were leptin resistant. These data indicate that a sex difference in central leptin remains in middle-aged rats, however since age-matched males were significantly heavier than the females, it remains to be determined whether the higher BW played a role. During the study females given the HF diet gained 20% in BW compared to their LF diet controls, while males on the HF diet gained 10% in BW compared to their LF diet controls. These results suggest that aged rats of both sexes are susceptible to diet-induced obesity and that middle-aged female rats remain sensitive to central leptin. doi:10.1016/j.appet.2010.04.141
The hunting of the snark. Interpretive issues in neurobiological analysis of food-entrained circadian rhythms R.E. MISTLBERGER Simon Fraser University, Burnaby, BC, Canada When food is freely available, feeding behavior in mammals is controlled by a circadian clock (the suprachiasmatic nucleus) entrained by daily light–dark cycles. When food is temporally restricted, food seeking behavior comes under control of a separate circadian mechanism entrained to mealtime. The physical location, inputs, outputs and molecular basis of this food-entrainable mechanism have proven difficult to establish and remain contentious, but as this symposium will show, progress has been made. I will discuss interpretive issues in evaluating the effects of lesions and gene manipulations on food-entrained rhythms in rats and mice, with a special focus on the role of the dorsomedial hypothalamus and known circadian clock genes. doi:10.1016/j.appet.2010.04.142
Butorphanol effects on feeding and neuropeptide Y gene expression in the rat A. MITRA 1,∗ , B.A. GOSNELL 1 , C.M. KOTZ 2 , E.M. KIM 2 , M.K. GRACE 2 , C.J. BILLINGTON 2 , A.S. LEVINE 1 1 Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA 2 Veterans Affairs Medical Center, Minneapolis, MN, USA, 3 Minn. Obesity Center, University of Minnesota, St. Paul, MN, USA Butorphanol ([BT] an opioid receptor agonist) is different from other opioid agonists in that a single dose of BT can elicit up to 12 g of chow intake in a satiated rat whereas most opioid agonists induce a mild feeding response (2–3 g). Here, we first examined whether the effectiveness of BT to elicit feeding was affected by dose, time of day, and method of infusion and possible tachyphylaxis following administration. Secondly, we examined whether BT administration influenced hypothalamic NPY gene expression and peptide levels. A single dose administration of BT (4 or 16 mg/kg) significantly increased food intake at 2, 4 and 6 h after administration. However following repeated injections of BT at 4 mg/kg, the cumulative long-term intake of BT-treated rats did not differ from that of controls, indicating that the animals compensate for the increased feeding following BT injection by decreased feeding at a later time. An ascending dose schedule of repeated BT injections resulted in additional feeding. NPY gene expression in the ARC was influenced by feeding status but not by BT. The amount of food consumed and the level of NPY mRNA were inversely correlated. This is consistent with NPYs role in normal feeding. We conclude that the feeding produced by BT is sensitive to dose and dosing paradigm. Further, its mechanism of action does not appear to be mediated by NPY pathways. This work was supported by the VAMC, NIH DK42698, NIDA DA03999 and NIDCR T32DE007288. doi:10.1016/j.appet.2010.04.143