Weight Loss and High-Protein, High-Fiber Diet Consumption Impact Blood Metabolite Profiles, Body Composition, Voluntary Physical Activity, Fecal Microbiota, and Fecal Metabolites of Adult Dogs

Canine obesity is associated with reduced lifespan and metabolic dysfunction, but can be managed by dietary intervention. This study aimed to determine the effects of restricted feeding of a high-protein, high-fiber (HPHF) diet and weight loss on body composition, physical activity, blood metabolites, and fecal microbiota and metabolites of overweight dogs. Twelve spayed female dogs [age: 5.5±1.1 yr; body weight (BW): 14.8±2.0 kg, body condition score (BCS): 7.9±0.8] were fed a HPHF diet during a 4-wk baseline phase to maintain BW. After baseline (wk 0), dogs were first fed 80% of baseline intake and then adjusted to target 1.5% weekly weight loss for 24 wk. Body composition using dual-energy x-ray absorptiometry and blood samples (wk 0, 6, 12, 18, 24), voluntary physical activity (wk 0, 7, 15, 23), and fresh fecal samples for microbiota and metabolite analysis (wk 0, 4, 8, 12, 16, 20, 24) were measured over time. Microbiota data were analyzed using QIIME 2. All data were analyzed statistically over time using SAS 9.4. After 24 wk, dogs lost 31.2% of initial BW and had 1.43±0.73% weight loss per wk. BCS decreased (P<0.0001) by 2.7 units, fat mass decreased (P<0.0001) by 3.1 kg, and fat percentage decreased (P<0.0001) by 3.1 kg and 11.7% with weight loss. Many serum metabolites and hormones were altered, with triglycerides, leptin, insulin, C-reactive protein, and interleukin-6 decreasing (P<0.05) with weight loss. Relative abundances of fecal Bifidobacterium, Coriobacteriaceae UCG-002, undefined Muribaculaceae, Allobaculum, Eubacterium, Lachnospira, Negativivibacillus, Ruminococcus gauvreauii group, uncultured Erysipelotrichaceae, and Parasutterella increased (P<0.05), whereas Prevotellaceae Ga6A1 group, Catenibacterium, Erysipelatoclostridium, Fusobacterium, Holdemanella, Lachnoclostridium, Lactobacillus, Megamonas, Peptoclostridium, Ruminococcus gnavus group, and Streptococcus decreased (P<0.01) with weight loss. Despite the number of significant changes, a state of dysbiosis was not observed in overweight dogs. Fecal ammonia and secondary bile acids decreased, while fecal valerate increased with weight loss. Several correlations between gut microbial taxa and biological parameters were observed. Our results suggest that restricted feeding of a HPHF diet and weight loss promotes fat mass loss, minimizes lean mass loss, reduces inflammatory marker and triglyceride concentrations, and modulates fecal microbiota phylogeny and activity in overweight dogs.

A reduction in voluntary physical activity in early pregnancy in mice is mediated by prolactin

As part of the maternal adaptations to pregnancy, mice show a rapid, profound reduction in voluntary running wheel activity (RWA) as soon as pregnancy is achieved. Here, we evaluate the hypothesis that prolactin, one of the first hormones to change secretion pattern following mating, is involved in driving this suppression of physical activity levels during pregnancy. We show that prolactin can acutely suppress RWA in non-pregnant female mice, and that conditional deletion of prolactin receptors (Prlr) from either most forebrain neurons or from GABA neurons prevented the early pregnancy-induced suppression of RWA. Deletion of Prlr specifically from the medial preoptic area, a brain region associated with multiple homeostatic and behavioural roles including parental behaviour, completely abolished the early pregnancy-induced suppression of RWA. As pregnancy progresses, prolactin action continues to contribute to the further suppression of RWA, although it is not the only factor involved. Our data demonstrate a key role for prolactin in suppressing voluntary physical activity during early pregnancy, highlighting a novel biological basis for reduced physical activity in pregnancy.

Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns

Motivational symptoms such as anergia, fatigue, and reduced exertion of effort are seen in depressed people. To model this, nucleus accumbens (Nacb) dopamine (DA) depletions are used to induce a low-effort bias in rodents tested on effort-based decision-making. We evaluated the effect of the catecholamine uptake blocker bupropion on its own, and after administration of tetrabenazine (TBZ), which blocks vesicular storage, depletes DA, and induces depressive symptoms in humans. Male CD1 mice were tested on a 3-choice-T-maze task that assessed preference between a reinforcer involving voluntary physical activity (running wheel, RW) vs. sedentary activities (sweet food pellet intake or a neutral non-social odor). Mice also were tested on the forced swim test (FST), two anxiety-related measures (dark–light box (DL), and elevated plus maze (EPM)). Expression of phosphorylated DARPP-32 (Thr34 and Thr75) was evaluated by immunohistochemistry as a marker of DA-related signal transduction. Bupropion increased selection of RW activity on the T-maze. TBZ reduced time running, but increased time-consuming sucrose, indicating an induction of a low-effort bias, but not an effect on primary sucrose motivation. In the FST, bupropion reduced immobility, increasing swimming and climbing, and TBZ produced the opposite effects. Bupropion reversed the effects of TBZ on the T-maze and the FST, and also on pDARPP32-Thr34 expression in Nacb core. None of these manipulations affected anxiety-related parameters. Thus, bupropion improved active behaviors, which were negatively motivated in the FST, and active behaviors that were positively motivated in the T-maze task, which has implications for using catecholamine uptake inhibitors for treating anergia and fatigue-like symptoms.

Histochemical Characterisation and Gene Expression Analysis of Skeletal Muscles from Maremmana and Aubrac Steers Reared on Grazing and Feedlot Systems

This study aimed to characterise the fibre composition of Triceps brachii (TB) and Semimembranosus (SM) muscles from 20 Maremmana (MA) and 20 Aubrac (AU) steers, and the effect of grazing activity in comparison with feedlot system. The histochemical method was performed with the m-ATPase method with an acid pre-incubation, thus allowing to distinguish type I, IIA, and IIB fibres. Additionally, on total RNA extracted from SM muscle, the expressions of atp1a1, mt-atp6, and capn1 genes were evaluated, in order to find potential associations with muscle fibre histochemical characteristics. In SM muscle, the MA steers had the greater frequency of oxidative fibres (type I and IIA) and the higher atp1a1 expression, in comparison to AU steers. Conversely, AU steers had a greater frequency of type IIB fibres, and the higher capn1 expression. A similar histochemical pattern was observed in TB muscle. The grazing activity was probably insufficient to determine differences both for fibre proportion and size, and gene expressions, except for mt-atp6 expression that was surprisingly highest in feedlot MA in comparison to other steers. These findings further the knowledge of muscle properties belonging to these breeds, and the effect of voluntary physical activity since few studies were available in this regard.

Changes in Behaviour and Voluntary Physical Activity Exhibited by Sled Dogs throughout Incremental Exercise Conditioning and Intermittent Rest Days

Participation in repetitive endurance training decreases sled dogs’ voluntary activity and locomotive behaviours; however, the changes in their voluntary physical activity over consecutive rest days has not been examined to assess exercise-recovery. The objective of this study was to examine the changes in behaviour and voluntary activity of sled dogs throughout repetitive incremental conditioning and intermittent rest days. Fourteen dogs (6 males, 8 females; age 3.7 ± 2.7 years; BW 21.5 ± 2.8 kg) underwent 10 weeks of conditioning. Once a week, 5-min video recordings were taken pre- and post-exercise to measure the time spent performing agonistic behaviours, chewing on the gangline, digging, jumping, lunging, posture changing, sitting, standing and lying. Additionally, voluntary physical activity was measured on a day with an exercise bout during baseline, week 4, 5 and 7 and two consecutive rest days during baseline, week 1, 4, 5 and 7. A repeated-measures mixed model was used to analyse data in SAS (v 9.4.). As dogs progressed through their conditioning, the time spent changing posture prior to an exercise bout decreased (p < 0.05), suggesting that dogs may reduce their voluntary locomotive behaviours with increasing exercise. Additionally, dogs were more active during the second consecutive rest day than the first (p < 0.05), suggesting that rest days may provide a short-term recovery period.

Voluntary wheel running is effective on suppressing of obesity but not on blood pressure and insulin resistance in female rats fed with high fructose diet

A fructose-rich diet has been known to cause metabolic syndrome effects such as body weight gain, increased blood pressure, blood lipids and glucose levels. The role of voluntary physical activity in these alterations is not known clearly. The aim of this study was to investigate the possible improving effects of voluntary physical activity in rats that were feeding with a fructose-rich diet. Spraque-Dawley female rats were separated as control (C;n=7), voluntary physical activity (A;n=7), fructose (F;n=7) and fructose+activity (F+A;n=7) groups. A and FA groups were kept in cages with running wheels during six weeks. F and FA groups were fed with adding 20% fructose in drinking water. Body weight was measured weekly and Lee Index was used to determine obesity. At the end of the feeding period serum glucose, insulin and lipid levels were measured by enzymatic method and blood pressure was determined with the tail-cuff method. Daily voluntary walking distance in F+A and A groups were similar during six weeks. Fructose intake induced to increase systolic blood pressure (p=0.001), diastolic blood pressure (p=0.002), glucose (p=0.041), insulin (p=0.001), cholesterol (p=0.001), triglyceride (p=0.001) and liver weight (p=0.035). The voluntary activity was found effective on the decrease of weight gain (p=0.018) however we did not observe a significant effect on blood pressure (p=0.917) and insulin resistance (p=0.565) following the fructose-rich diet. We conclude that voluntary activity has preventive effect on obesity but may not to be effective on increased blood pressure and insulin resistance in female rats which were feeding fructose-rich diet during six weeks.

Voluntary physical activity protects against olanzapine-induced hyperglycemia

Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off‐label" conditions. While effective in reducing psychoses, OLZ causes rapid impairments in glucose and lipid homeostasis. The purpose of this study was to investigate if voluntary physical activity via wheel running (VWR) would protect against the acute metabolic side effects of OLZ. Male C57BL/6J mice remained sedentary or were provided with running wheels overnight, prior to treatment with OLZ either at the beginning of the light cycle, or 7 or 24 hours following the cessation of VWR. Prior VWR protected against OLZ-induced hyperglycemia immediately and 7 hours following a bout of overnight wheel running. Protection against, hyperglycemia immediately following VWR was associated with increased insulin tolerance and an attenuated OLZ-induced increase in the serum glucagon:insulin ratio. The protective effect of VWR against OLZ-induced increases in hyperglycemia and glucagon:insulin ratio were maintained in high fat fed, and AMPK b1 deficient mice, models which display a potentiated OLZ-induced increase in blood glucose. Repeated OLZ treatment did not impair VWR performance and protection against the acute effects of OLZ on blood glucose was present after 1 week of daily OLZ treatment in mice given access to running wheels. In contrast to the effects on glucose metabolism, VWR, for the most part, did not impact OLZ induced perturbations in lipolysis, liver triglyceride accumulation or whole-body substrate oxidation. Collectively our findings demonstrate the efficacy of voluntary physical activity as an approach to protect against OLZ-induced impairments in glucose metabolism.

Analysis of Activity-Dependent Energy Metabolism in Mice Reveals Regulation of Mitochondrial Fission and Fusion mRNA by Voluntary Physical Exercise in Subcutaneous Fat from Male Marathon Mice (DUhTP)

Physical inactivity is considered as one of the main causes of obesity in modern civilizations, and it has been demonstrated that resistance training programs can be used to reduce fat mass. The effects of voluntary exercise on energy metabolism are less clear in adipose tissue. Therefore, the effects of three different voluntary exercise programs on the control of energy metabolism in subcutaneous fat were tested in two different mouse lines. In a cross-over study design, male mice were kept for three or six weeks in the presence or absence of running wheels. For the experiment, mice with increased running capacity (DUhTP) were used and compared to controls (DUC). Body and organ weight, feed intake, and voluntary running wheel activity were recorded. In subcutaneous fat, gene expression of browning markers and mitochondrial energy metabolism were analyzed. Exercise increased heart weight in control mice (p < 0.05) but significantly decreased subcutaneous, epididymal, perinephric, and brown fat mass in both genetic groups (p < 0.05). Gene expression analysis revealed higher expression of browning markers and individual complex subunits present in the electron transport chain in subcutaneous fat of DUhTP mice compared to controls (DUC; p < 0.01), independent of physical activity. While in control mice, voluntary exercise had no effect on markers of mitochondrial fission or fusion, in DUhTP mice, reduced mitochondrial DNA, transcription factor Nrf1, fission- (Dnm1), and fusion-relevant transcripts (Mfn1 and 2) were observed in response to voluntary physical activity (p < 0.05). Our findings indicate that the superior running abilities in DUhTP mice, on one hand, are connected to elevated expression of genetic markers for browning and oxidative phosphorylation in subcutaneous fat. In subcutaneous fat from DUhTP but not in unselected control mice, we further demonstrate reduced expression of genes for mitochondrial fission and fusion in response to voluntary physical activity.

PSXI-33 Effects of weight loss and feeding a high-protein, high-fiber diet on blood metabolite profiles, body composition and voluntary physical activity in overweight dogs

Canine obesity can be managed by dietary energy restriction using a specifically formulated weight loss diet. The objective of this study was to determine the effects of weight loss on body composition, voluntary physical activity, and blood metabolites of overweight dogs while being fed a high-protein, high-fiber diet. All procedures were approved by the University of Illinois Institutional Animal Care and Use Committee prior to experimentation. Twelve overweight adult spayed female dogs (BW: 15.3±2.1 kg, BCS: 8.1±0.6) were fed a high-protein (CP: 42.0% DMB), high-fiber (TDF: 22.0% DMB) diet during a 5-wk baseline phase (wk 0) to identify food intake needed to maintain BW. A 24-wk weight loss phase followed. After wk 0, food was initially provided at 80% the amount needed to maintain BW and then adjusted weekly with a goal of 1.5–2% weight loss per wk. Data were analyzed statistically overtime using SAS 9.4. After 24 wk, dogs lost 31.2% of initial BW (P &lt; 0.0001), with 1.4±0.7% weight loss per wk. BCS decreased by 2.8 units (P &lt; 0.0001). During weight loss, dogs consumed an average of 457.5±61.4 kcal/d, with energy intake being reduced by a total of 43.8% by wk 24 compared to baseline. Lean muscle mass, fat mass, and fat percentage were reduced (P &lt; 0.0001) by 1.3 kg, 3.1 kg, and 11.7% respectively. Serum triglycerides, alkaline phosphatase, white blood cell counts, and neutrophils were decreased (P &lt; 0.0001), but serum bilirubin, creatinine, and blood urea nitrogen were increased (P &lt; 0.01) over time. Average daily physical activity changed over time, but was not greatly different due to weight loss. Our results suggest that a high-protein, high-fiber diet promotes fat mass loss, minimizes lean muscle mass loss, and reduces inflammatory marker and triglyceride concentrations in overweight dogs. Therefore, it is a suitable nutritional solution for weight loss programs in dogs.