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1.
Biol Reprod ; 91(6): 141, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25320149

ABSTRACT

Cells in the medial preoptic area (mPOA), arcuate nucleus (ARC), and ventromedial nucleus (VMN) that possess estrogen receptor alpha (ER alpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of ER alpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to investigate the location of c-Fos, a marker for activation, in cells containing ER alpha or SST at various times during the follicular phase and to determine whether lipopolysaccharide (LPS) administration, which leads to disruption of the luteinizing hormone (LH) surge, is accompanied by altered ER alpha and/or SST activation patterns. Follicular phases were synchronized with progesterone vaginal pessaries, and control animals were killed at 0, 16, 31, and 40 h (n = 4-6/group) after progesterone withdrawal (PW [time 0]). At 28 h, other animals received LPS (100 ng/kg) and were subsequently killed at 31 h or 40 h (n = 5/group). Hypothalamic sections were immunostained for c-Fos and ER alpha or SST. LH surges occurred only in control ewes with onset at 36.7 ± 1.3 h after PW; these animals had a marked increase in the percentage of ER alpha cells that colocalized c-Fos (%ER alpha/c-Fos) in the ARC and mPOA from 31 h after PW and throughout the LH surge. In the VMN, %ER alpha/c-Fos was higher in animals that expressed sexual behavior than in those that did not. SST cell activation in the ARC and VMN was greater during the LH surge than in other stages in the follicular phase. At 31 or 40 h after PW (i.e., 3 or 12 h after treatment, respectively), LPS decreased %ER alpha/c-Fos in the ARC and the mPOA, but there was no change in the VMN compared to that in controls. The %SST/c-Fos increased in the VMN at 31 h after PW (i.e., 3 h after LPS) with no change in the ARC compared to controls. These results indicate that there is a distinct temporal pattern of ER alpha cell activation in the hypothalamus during the follicular phase, which begins in the ARC and mPOA at least 6-7 h before the LH surge onset and extends to the VMN after the onset of sexual behavior and LH surge. Furthermore, during the surge, some of these ER alpha-activated cells may be SST-secreting cells. This pattern is markedly altered by LPS administered during the late follicular phase, indicating that the disruptive effects of this stressor are mediated by suppressing ER alpha cell activation at the level of the mPOA and ARC and enhancing SST cell activation in the VMN, leading to the attenuation of the LH surge.


Subject(s)
Arcuate Nucleus of Hypothalamus/metabolism , Estrogen Receptor alpha/metabolism , Lipopolysaccharides/pharmacology , Neurons/physiology , Preoptic Area/metabolism , Somatostatin/metabolism , Ventromedial Hypothalamic Nucleus/metabolism , Animals , Female , Follicular Phase/drug effects , Neurons/drug effects , Sexual Behavior, Animal/drug effects , Sexual Behavior, Animal/physiology , Sheep/physiology
2.
J Nutr Sci ; 3: e45, 2014.
Article in English | MEDLINE | ID: mdl-26101613

ABSTRACT

Canine obesity is a prevalent disease, but many owners are unaware of it, partly due to misperception of their dog's body shape. Body condition scoring (BCS) is a simple method of assessing body composition, but whether it can reduce owner misperception is unclear. Our aim was to determine the effect of a BCS system on owners' ability to estimate the body condition of their dog. Information from 110 dog owners attending three UK veterinary practices was gathered, by interview, between March and April 2013. First, owners were asked to determine their dog's body condition without guidance, and then reassess it using a five-point BCS chart. Most owners (85/110, 77 %) believed the chart to have improved their ability to estimate the condition of their dog correctly. However, only a weak agreement existed between owner estimates and those of the primary investigator, both with (kappa (κ) = 0·28; P < 0·001) and without (κ = 0·32; P < 0·001) the BCS chart. Furthermore, most owners incorrectly estimated their dog's body condition, both with (71/110; 64 %) and without (72/110; 65 %) the chart (P = 1·00), with underestimation being most common (with = 63/71, 89 %; without = 66/72, 92 %; P = 0·57). Owners of overweight dogs more commonly misperceived their dog's body condition, both with (BCS 1-3: 5/35, 14 %; BCS 4-5: 64/75, 85 %; P < 0·001) and without (BCS 1-3: 10/35, 28 %; BCS 4-5: 61/75, 81 %; P < 0·001) the BCS chart. Thus, use of a five-point BCS chart does not improve accuracy of owners' perception of their dog's body shape, despite the accompanying perception that it does.

3.
Br J Nutr ; 109(9): 1573-89, 2013 May.
Article in English | MEDLINE | ID: mdl-23433235

ABSTRACT

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly,neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether n-3 PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.


Subject(s)
Diet , Energy Metabolism , Neurogenesis , Adult , Humans
4.
Nutr Metab (Lond) ; 4: 15, 2007 Jun 14.
Article in English | MEDLINE | ID: mdl-17570846

ABSTRACT

BACKGROUND: Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats. METHODS: Male Wistar rats (n = 6/group) were fed diets providing varying percentages of energy from fat and carbohydrate (CHO). For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO), chow supplemented with chocolate biscuit (30% fat; 56% CHO) or a high-fat diet (45% fat; 35% CHO). Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA). RESULTS: Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p < 0.01) and elevated concentrations of TGs and NEFAs (+41% and +17%; both p < 0.05). High-fat-fed animals showed an increase only in NEFAs (+38%; p < 0.01). Arterial vasoconstriction in response to NA and KCl increased only in biscuit-fed rats (both p < 0.01), while vasorelaxation in response to CCh and SNP, but not histamine, was attenuated in both groups (both p < 0.01). Furthermore, whereas the effect of the high-fat diet was most pronounced in endothelium-dependent vasorelaxation, the biscuit diet had the greater effect on endothelium-independent vasorelaxation. CONCLUSION: Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.

5.
Br J Pharmacol ; 144(3): 308-16, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15655531

ABSTRACT

In 6- and 10-week-old obesity-prone (fa/fa) Zucker diabetic fatty (ZDF) rats, effects of prevention and intervention therapies, respectively, were compared between PPARalpha/gamma agonist, ragaglitazar (RAGA) and separate PPARgamma and alpha agonists, pioglitazone (PIO) and bezafibrate (BF). In a separate study, lean (+/+) ZDF rats fed highly palatable chow to induce dietary obesity and insulin resistance were treated similarly. To test insulin-secretory capacity, all animals underwent a hyperglycaemic clamp. Insulin sensitivity was improved equally by RAGA and PIO in fa/fa rats subjected to both prevention and intervention treatments (e.g., prevention HOMA-IR: -71 and -72%, respectively), as was hyperglycaemia (both -68%). BF had no effect on either parameter in any study. Plasma lipids were markedly reduced (by 48-77%) by RAGA in all studies, equivalent to PIO, but to a greater extent than BF. RAGA improved beta-cell function (HOMA-beta) more than three-fold with prevention and intervention therapies, whereas PIO showed improvement only in intervention therapy. Consistent with improved insulin sensitivity, glucose infusion rate during the clamp was 60% higher in RAGA-treated animals subjected to prevention therapy, but there was little additional insulin-secretory response, suggesting that insulin secretion was already maximal.Thus, RAGA and PIO equally improve metabolic profile in ZDF rats, particularly when administered early in the course of diabetes. They also improve beta-cell function, although this is better demonstrated through indices incorporating fasting insulin and glucose concentrations than through the hyperglycaemic clamp technique in this model.


Subject(s)
Diabetes Mellitus/metabolism , Hypoglycemic Agents/pharmacology , Insulin Resistance/physiology , Obesity/metabolism , Oxazines/pharmacology , PPAR alpha/agonists , PPAR gamma/agonists , Phenylpropionates/pharmacology , Thiazolidinediones/pharmacology , Adipose Tissue/physiology , Animals , Bezafibrate/pharmacology , Body Composition/drug effects , Body Weight/drug effects , Diabetes Mellitus/genetics , Diet , Energy Metabolism/drug effects , Glucose Clamp Technique , Hypolipidemic Agents/pharmacology , Insulin/metabolism , Obesity/blood , Organ Size/drug effects , Pancreas/metabolism , Pioglitazone , Rats , Rats, Inbred Strains , Receptors, Cell Surface/genetics , Receptors, Leptin
6.
Clin Sci (Lond) ; 105(4): 403-8, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12780342

ABSTRACT

Adiponectin levels are decreased in subjects with obesity, diabetes and coronary artery disease. In the present study, we have investigated whether the decrease in the levels and mRNA expression of adiponectin is due to obesity or to the diet itself. Wistar rats were either fed standard laboratory chow throughout (controls) or given a fat-enriched, glucose-enriched diet (diet-fed) for 2 days or 16 weeks. After 2 days of diet feeding, total body weight, fat pad masses and the plasma levels of glucose, insulin and leptin were all comparable between the two groups, while plasma NEFA (non-esterified fatty acid) and triacylglycerol levels were increased in the diet-fed animals (P<0.01 for both). There was a marked (P<0.01) decrease in plasma adiponectin levels. After 16 weeks of diet feeding, diet-fed rats had significantly higher body weight, fat pad mass and plasma levels of leptin, adiponectin, NEFA and triacylglycerol (P<0.001 for all) compared with chow-fed controls, whereas plasma levels of glucose and insulin were similar in the two groups. After 2 days of diet feeding, there were no significant changes in Ob mRNA levels in epididymal fat, whereas there was a marked decrease in adiponectin mRNA levels. After 16 weeks of diet feeding, rats had significantly increased levels of Ob mRNA, but decreased adiponectin mRNA levels, in epididymal fat compared with the chow-fed group (P<0.001 for both). These findings suggest that obesity per se is not a factor in the decreased adiponectin levels observed in obese subjects. We propose that the lipid profile of the plasma and/or the constituents of the diet consumed by rats may contribute to adiponectin levels more than obesity per se.


Subject(s)
Adipose Tissue/metabolism , Dietary Fats/administration & dosage , Dietary Sucrose/administration & dosage , Intercellular Signaling Peptides and Proteins , Proteins/genetics , RNA, Messenger/metabolism , Adiponectin , Animals , Blood Glucose/analysis , Epididymis , Fatty Acids, Nonesterified/blood , Insulin/blood , Leptin/blood , Leptin/genetics , Male , RNA, Messenger/analysis , Rats , Rats, Wistar , Triglycerides/blood
7.
Int J Exp Pathol ; 84(2): 83-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12801282

ABSTRACT

The Zucker Diabetic Fatty (ZDF) rat is a model of impaired insulin sensitivity arising from hyperphagia owing to a mutation in the leptin receptor. In time, young ZDF rats, which are not initially diabetic, develop impaired pancreatic beta-cell function leading to apoptotic cell death. This results in an inability to fully compensate for the reduction in insulin sensitivity with hypersecretion of insulin. Young, pre-diabetic ZDF rats were treated, over a 4-week period, with the thiazolidinedione compound MCC-555, and the islet morphology studied in comparison to ZDF rats not given MCC-555. In particular, changes in the apoptotic incidence, as measured using TUNEL staining to localize apoptotic cells, were studied over the 4-week period. Changes in the induction of nitric oxide synthase and in the accumulation of nitrate/nitrite within the pancreas were also studied during the time course of administration of MCC-555. The study has demonstrated that the administration of MCC-555 significantly decreases the apoptotic incidence in the islets of Langerhans of pre-diabetic ZDF rats given the compound, as compared to those not given MCC-555, as well as decreasing the accumulation of nitrate/nitrite within the pancreas.


Subject(s)
Apoptosis/drug effects , Diabetes Mellitus, Experimental/drug therapy , Islets of Langerhans/pathology , Nitric Oxide Synthase/metabolism , Thiazoles/therapeutic use , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/enzymology , Diabetes Mellitus, Type 2/pathology , Drug Administration Schedule , Insulin/blood , Islets of Langerhans/enzymology , Male , Rats , Rats, Zucker , Thiazolidinediones
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