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While obesity and type 2 diabetes (T2D) are associated with altered dopaminergic activity in the central nervous system and in adipose tissue (AT), the directions and underlying mechanisms remain inconclusive. Therefore, we characterized changes in the abundance of dopamine, its metabolites, and receptors DRD1 and DRD2 in the brain and AT upon dietary intervention or obesity. Male Wistar rats were fed either a standard pellet diet, a cafeteria diet inducing obesity and insulin resistance, or a calorie-restricted diet for 12 weeks. Abundance of dopamine and its receptors DRD1 and DRD2 were examined in brain regions relevant for feeding behavior and energy homeostasis. Furthermore, DRD1 and DRD2 protein levels were analyzed in rat inguinal and epidydimal AT and in human subcutaneous and omental AT from individuals with or without obesity. Rats with diet-induced obesity displayed higher dopamine levels, as well as DRD1 or DRD2 receptor levels in the caudate putamen and the nucleus accumbens core. Surprisingly, caloric restriction induced similar changes in DRD1 and DRD2, but not in dopamine levels, in the brain. Both diets reduced DRD1 abundance in inguinal and epidydimal AT, but upregulated DRD2 levels in inguinal AT. Furthermore, in human obesity, DRD1 protein levels were elevated only in omental AT, while DRD2 was upregulated in both omental and subcutaneous AT. These findings highlight dopaminergic responses to changes in energy balance, occurring both in the brain and AT. We propose that dopaminergic pathways are involved in tissue crosstalk during the development of obesity and T2D.

This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square fieldTM (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (p < 0.001) and increased adipose tissue weight in comparison to the control (p < 0.001) and restricted (p < 0.001) groups. Glucose was significantly increased (p < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (p < 0.01; p < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (p < 0.01) and restricted (p < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (p < 0.001; p < 0.05) and restricted (p < 0.001; p < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development.

Insects are often reared as a potential source of protein, both for human and animal consumption. However, food safety is a main concern and one common way of reducing the microbial load in insects is fasting them for 24-48 h. Fasting may pose a physiological stress with potential implications for welfare. Another parameter that can be manipulated in insect rearing facilities is the photoperiod, which affects maturation of the insects, and possibly immunity. In this study, adult Acheta domesticus of both sexes, reared in either 16 (16L:8D) or 12 h (12L:12D) of light, were fasted for 48 h or fed ad libitum prior to euthanasia. The immune parameters phenoloxidase (PO) activity, lysozyme concentration, haemocyte number and total protein content were investigated in haemolymph. The results revealed effects of both photoperiod and fasting on immunocompetence. Fasting lowered PO activity (p = 0.002) and haemocyte count (p = 0.005). The haemocyte count was especially affected by fasting in female crickets, and haemocyte count was correlated to protein concentration, and to PO activity in crickets reared in 16L:8D. A 16L:8D photoperiod lowered the protein content in haemolymph compared to 12L:12D (p = 0.045). Protein content has been correlated to disease resistance in previous studies, and was herein found to be correlated with PO activity. These results need to be replicated and investigated further to make recommendations for future cricket rearing, but the results point to the fact that rearing practices could have consequences for insect immunity.

Purpose: Obesity is associated with neuroendocrine and metabolic dysregulation, yet the underlying mechanisms remain incompletely understood. This study aimed to investigate how pituitary hormonal axes and peripheral hormones respond to a cafeteria diet or a calorie-restricted diet in rats.

Methods: Ten-week-old male Wistar rats (n = 36) were randomized (1:1:1) to one of three diets for 12 weeks: an ad libitum standard rat chow diet (control group); an ad libitum cafeteria diet, containing cheese doodles, chocolate balls and salted peanuts, in addition to standard chow (diet-induced obesity group, DIO); or calorie-restriction (aiming at 85% body weight of controls; restricted group). We assessed endocrine gland weights, plasma levels of pituitary hormones and related peripheral signals, and explored their associations with metabolic and behavioral outcomes.

Results: While the DIO group exhibited increased body weight, insulin resistance, and altered metabolic markers, only modest changes in pituitary hormones were observed, with a reduction in luteinizing hormone (p < 0.05). Correlation analysis showed that when combining the control and DIO groups, prolactin inversely correlated with exploratory-activity (rho =-0.458, p < 0.05) from the behavioral test. In contrast, the restricted group showed more pronounced hormonal changes, including reduced levels of adrenocorticotropic hormone (p < 0.01), prolactin, and thyroid-stimulating hormone (both p < 0.05) as well as insulin-like growth factor-1 (p < 0.01). Multivariate data analysis showed a clear separation of the DIO group from the other groups, mainly driven by metabolic variables.

Conclusion: Despite notable metabolic perturbations in the DIO group, the absence of endocrine changes suggests a partly different phenotype than what is typically observed in humans with obesity.

Introduction: Decision-making requires individuals to perceive probabilities and risks associated with different options. The Iowa gambling task (IGT) is a widely used instrument that assesses decision-making under uncertainty and risk by varying monetary reinforcer/loss contingencies. The rat gambling task (rGT), based on the IGT, is a preclinical test using varying number of palatable reinforcers as wins and different duration of timeouts as punishment, mimicking losses. The rGT requires extensive operant training prior to the free choice sessions. The aim of the present study was to investigate if task acquisition and number of training days affected subsequent individual differences in decision-making strategies in the rGT, and if behavioral profiles impacted on task learning.

Method: Training time and performance of 70 male Lister Hooded rats from previously published studies were herein used to investigate whether learning time affected later decision-making strategies in the free choice rGT. Behavioral profiles generated from a subset of animals were used to study the impact of underlying behavior on learning time.

Results: There were differences in training days between fast, intermediate and slow learners. However, time required to acquire the rGT did not affect subsequent decision-making strategies in the free choice rGT. Finally, learning time was independent of underlying behavioral profiles.

Discussion: In conclusion, neither decision-making strategies in the rGT nor behavioral profiles were correlated or differed between animals with different learning speed. This suggests that the large variation in training time between animals is unrelated to subsequent decision-making strategies during free choice rGT. Such information is valuable for researchers using the rGT.

One of the main challenges in analyzing chemical messengers in the brain is the optimization of tissue sampling and preparation protocols. Limiting postmortem time and terminating enzyme activity is critical to identify low-abundance neurotransmitters and neuropeptides. Here, we used a rapid and uniform conductive heat transfer stabilization method that was compared with a conventional fresh freezing protocol. Together with a selective chemical derivatization method and an optimized quantitation approach using deuterated internal standards, we spatially mapped neurotransmitters and their related metabolites by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in rat brain tissue sections. Although the heat stabilization did not show differences in the levels of dopamine, norepinephrine, and serotonin, their related metabolites 3,4-dihydroxyphenylacetaldehyde, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylacetaldehyde, dihydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid were all significantly lower, indicating reduced neurotransmitter postmortem turnover ratios. Heat stabilization enabled detection of an increased number and higher levels of prodynorphin, proenkephalin, and tachykinin-derived bioactive neuropeptides. The low-abundant C-terminal flanking peptide, neuropeptide-gamma, and nociceptin remained intact and were exclusively imaged in heat-stabilized brains. Without heat stabilization, degradation fragments of full-length peptides occurred in the fresh frozen tissues. The sample preparation protocols were furthermore tested on rat brains affected by acute anesthesia induced by isoflurane and medetomidine, showing comparable results to non-anesthetized animals on the neurotransmitters level without significant changes. Our data provide evidence for the potential use of heat stabilization prior to MALDI-MSI analyses to improve the examination of the in vivo state of neuronal chemical messengers in brain tissues not impacted by prior acute anesthesia.

Increasing levels of physical inactivity is a global burden for mankind and is also an emerging problem in companion dogs. In both humans and dogs, insufficient physical activity is associated with increased risk for noncommunicable diseases and impaired quality of life (QoL). The aim of the current pilot study was to evaluate effects of a joint outdoor exercise program for dog owners (n = 22) and dogs (n = 22) with focus on QoL and body measurements. Results indicate that an eight-week exercise intervention alone, with a target distance of at least 2 km twice a week, may be sufficient to significantly increase self-reported QoL and acceptance of bodily appearance in dog owners despite no reductions in body measurements. In dogs, a significantly reduced body condition score (BCS) was registered, despite no considerable changes in feeding. The increased owner motivation for continued joint exercise suggests potential for lifestyle changes, which could be investigated in future studies including control groups and long-term follow-ups. The importance of the human-animal bond as a success factor for increased mutual physical activity and health benefits in both dog owners and dogs is recommended to be studied in a more in-depth manner.

Background

Research on the effects of physical exercise on canine body composition is limited. The aim of this study was to investigate the effects of a physical exercise programme on bodyweight, body condition score (BCS) and chest, abdominal and thigh circumferences in dogs. Twenty-one healthy dogs of different breeds exercised together with their owners during an eight-week programme consisting of jogging and strength exercises. Standardised measurements were performed in triplicates with a measuring tape on standing dogs. Chest circumference was measured at three anatomical locations, abdomen at two and thigh at one. Data on bodyweight, BCS (9-point scale) and circumferences were analysed with mixed model repeated measures analyses to evaluate changes after the programme and effects of target distance.

Results

Seven dog owners choose a target distance of 2 km and 14 owners choose 5-10 km. Mean BCS decreased (P = 0.007) after the programme (5.1 +/- 0.9 vs. 4.7 +/- 0.6) but there was no effect of target distance. Almost all chest and abdominal circumference measurements decreased (P <= 0.007) with the 2 km group driving the reduction in chest circumference and the 5-10 km group driving the reduction in abdominal circumference. In contrast, thigh circumference (28.8 +/- 0.4 vs. 30.2 +/- 0.4) increased (P = 0.007) while bodyweight was maintained. There were positive correlations between BCS and abdominal/chest ratios before and after the programme (Pearson correlation; R square <= 0.43, P <= 0.0012) but the mean ratio remained constant.

Conclusions

Results indicated a redistribution between total body fat and muscle mass in body composition of normal weight to slightly overweight dogs after the physical exercise programme. The use of bodyweight alone was not a reliable evaluation method to complement the BCS assessment. However, repeated measurements of chest, abdominal and thigh circumference might aid in the assessment of body composition in dogs performing physical exercise. Further research should include a control group and objective evaluations of total body fat and lean mass, in order to investigate the effectiveness of physical exercise as a freestanding method for decreasing BCS and increasing muscle mass in overweight dogs.

Purpose

We aimed to characterize the RYGB-induced changes in the dynamics of brain glucose uptake. We addressed heterogeneity between brain regions during experimental normo- and hypoglycemia and explored associations with anthropometric and metabolic outcomes of RYGB.

Methods

Analyses of regional brain glucose uptake were performed on 9 individuals with obesity and no diabetes, investigated with combined brain ¹⁸F-FDG-PET and fMRI during hyperinsulinemic normo- and hypoglycemic clamp, one month before and four months after RYGB. FDG clearance, reflecting glucose uptake rate, was assessed in 38 brain regions, covering all cortical areas and subcortical nuclei, during hyperinsulinemic normo- and hypoglycemia. Correlation analyses were performed to identify associations with other outcomes of RYGB.

Results

FDG uptake rate during hypoglycemia was higher than during normoglycemia in all brain regions, both before and after RYGB. Moreover, in most regions and especially in cortical areas involved in inhibitory behavioral control, FDG uptake rate tended to be reduced after surgery during normoglycemia but elevated during hypoglycemia. However, these post-surgical changes in FDG uptake rate were opposite in the hypothalamus. Thus, the hypo-to-normoglycemia FDG clearance ratio tended to increase in all brain regions following RYGB, but not in the amygdala and the hypothalamus. Changes in regional FDG uptake rate after RYGB during normoglycemia were associated with weight loss and improved systemic insulin sensitivity.

Conclusion

Using dynamic FDG-PET, we show region-specific patterns of changes in glucose utilization following RYGB. In the hypothalamus, glucose uptake during normoglycemia tended to rise after RYGB while it was reduced in cortical regions involved in behavioral control. Following RYGB, the hypothalamus and amygdala, in contrast to other regions, displayed trends of reduced glucose uptake during hypoglycemia. These pilot results highlight the brain effects of RYGB and suggest behavioral and neuroendocrine adaptations which contribute to its antidiabetic effects.

Introduction

Roux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.

Method

Ten patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.

Results

RS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.

Conclusion

RYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.