Fecal Energy Loss Research Articles

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice.

Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8weeks. After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.

Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects.

To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

Dietary Fatty Acid Composition Influences Energy Accretion in Rats

To study the influence of dietary fatty acid composition on energy metabolism, forty male rats were fed elemental diets containing 42% of energy as fish oil, safflower oil, olive oil or beef tallow for 12 wk. Food intakes and body weights were measured daily. Energy expenditure and body composition were determined using doubly labeled water on the final 2 d. Pooled fecal energy losses differed in response to dietary manipulation, with losses greatest in rats fed beef tallow and least in those fed olive oil. Higher lean body mass gains and lower fat mass gains were observed in rats fed diets containing fish oil, compared with rats fed olive oil or beef tallow. Total energy gains in rats fed olive oil (3632 +/- 145 kJ) and beef tallow (3850 +/- 136 kJ) were higher than those in rats fed fish oil (2905 +/- 196 kJ). Energy efficiency in both the olive oil and beef tallow groups was also higher than that in the fish oil group. There were no differences in energy expenditure measured by doubly labeled water technique among the four groups. The data suggest that dietary fatty acid composition alters the efficiency of energy substrate accretion in rats.

Standardized Complex Gut Microbiomes Influence Fetal Growth, Food Intake, and Adult Body Weight in Outbred Mice.

Obesity places a tremendous burden on individual health and the healthcare system. The gut microbiome (GM) influences host metabolism and behaviors affecting body weight (BW) such as feeding. The GM of mice varies between suppliers and significantly influences BW. We sought to determine whether GM-associated differences in BW are associated with differences in intake, fecal energy loss, or fetal growth. Pair-housed mice colonized with a low or high microbial richness GM were weighed, and the total and BW-adjusted intake were measured at weaning and adulthood. Pups were weighed at birth to determine the effects of the maternal microbiome on fetal growth. Fecal samples were collected to assess the fecal energy loss and to characterize differences in the microbiome. The results showed that supplier-origin microbiomes were associated with profound differences in fetal growth and excessive BW-adjusted differences in intake during adulthood, with no detected difference in fecal energy loss. Agreement between the features of the maternal microbiome associated with increased birth weight here and in recent human studies supports the value of this model to investigate the mechanisms by which the maternal microbiome regulates offspring growth and food intake.

Effects of Time-Restricted Feeding on Energy Balance: A Cross-Over Trial in Healthy Subjects.

Time-restricted feeding (TRF) has been recently reported as an effective dietary intervention for losing body weight, implying a negative energy balance, without restricting nutrient intake. However, the detailed energy balance alteration caused by TRF remains unclear. This study was a randomized controlled clinical trial using a within-subject cross-over design. Twelve healthy, normal-weighted volunteers (age: 24 ± 2.3 years; BMI: 21.9 ± 1.71 kg/m2; 7 females) were studied under a rigorous control for calorie intakes, physical activities as well as sleep-wake cycle to evaluate the energy balance systematically. Each participant consumed an isocaloric diet within either a 5.5-hour TRF or 11-hour control schedule. All energy intake and excretion were traced and collected and accessed by bomb calorimetry. Energy expenditure and substrates oxidation were monitored in a metabolic chamber. TRF compared with control schedule is associated with a 22.7% increase in fecal energy loss (Δ = 32.25 ± 9.33 Kcal, p = 0.005) and a trend in increasing 14.5% urine energy loss (Δ = 6.67 ± 3.14 Kcal, p = 0.058) without change energy expenditure. In total, a negative energy balance (Δ = -45.95 ± 19.00 Kcal, p = 0.034), which was equal to -2.6% of total energy intake, has been observed during TRF interventions. In the meantime, glycemic profiles, heart rate, respiration rate as well as metabolic flexibility were also improved during TRF intervention. Taken together, our findings unravel the mystery of how TRF regulates energy balance, supporting the use of TRF as an alternative dietary strategy for weight loss.

Energy value of hydrolyzed feather meal and flash-dried poultry protein for broiler chickens and pigs.

Three experiments were conducted to determine the metabolizable energy (ME) and nitrogen-corrected ME (MEn) contents of hydrolyzed feather meal (HFM) and flash-dried poultry protein (FDPP) for broiler chickens and to determine their digestible energy (DE) and ME for pigs. The energy-yielding ingredients in a reference diet (RD) were replaced at 0, 75, or 150g/kg by HFM in experiment (Exp.) 1; at 0, 75, or 150g/kg by FDPP in Exp. 2; and at 0, 150g/kg HFM, or 150g/kg FDPP in Exp. 3. Birds were fed a standard broiler starter diet from hatch to days 18 and 17 for respective Exp. 1 and 2, following which 144 birds (8 replicate cages of 6 birds per cage) were assigned to the three experimental diets in a randomized complete block design with body weight as the blocking factor. Experimental diets were fed for 5 d, and excreta were collected during the last 3 d. Twenty-four 20-kg barrows, individually housed in metabolic crates equipped with a feeder and drinker, were used in Exp. 3. The barrows were assigned to the three experimental diets in a randomized complete block design with body weight as a blocking factor. Following a 5-d adaptation period, feces and urine were collected for 5 d in a total collection method. Data were used to determine the regression-derived ME and MEn of HFM and FDPP for broiler chickens in Exp. 1 and 2, respectively. The DE and ME of HFM and FDPP for pigs in Exp. 3 were determined using the difference procedure. In Exp. 1, the inclusion of HFM linearly increased (P < 0.05) ME from 3,231 to 3,368 kcal/kg DM for 0 to 150g/kg replacement of RD. The total tract retention of DM and metabolizability of energy linearly increased (P < 0.05) as replacement of RD with FDPP increased from 0 to 150g/kg in Exp. 2. Inclusion of FDPP linearly increased (P < 0.01) ME from 3,425 to 3,591 kcal/kg DM. In Exp. 3, the diets containing 150g/kg HFM or FDPP induced greater (P < 0.05) fecal DM and energy losses than the RD; however, the digestibility of energy across the three experimental diets was not different. The respective regression-derived ME and MEn of hydrolyzed feather meal for broiler chickens in the current study were 4,250 and 3,745 kcal/kg DM with corresponding values of 4,710 and 4,081 kcal/kg DM for flash-dried poultry protein. In pigs, 4,783 and 4,405 kcal/kg DM were the respective DE and ME of hydrolyzed feather meal, and 4,553 and 4,320 kcal/kg DM were the corresponding estimates for flash-dried poultry protein.

Methodologies for energy evaluation of pig and poultry feeds: A review

The cost of feed represents an important part of the total cost in swine and poultry production (>60%) with energy accounting for at least 70% of feed cost. The energy value of ingredients or compound feeds can be estimated as digestible (DE), metabolisable (ME) and net energy (NE) in pigs and ME and NE in poultry. The current paper reviews the different methods for evaluating DE, ME and NE of feeds for monogastric animals and their difficulties and limits, with a focus on NE. In pigs and poultry, energy digestibility depends on the chemical characteristics of the feed, but also on technology (pelleting, for instance) and animal factors such as their health and body weight. The ME value includes the energy losses in urine that are directly dependent on the proportion of dietary N excreted in urine resulting in the concept of ME adjusted for a zero N balance (MEn) in poultry. For poultry, the concept of true ME (TME, TMEn), which excludes the endogenous fecal and urinary energy losses from the excreta energy, was also developed. The measurement of dietary NE is more complex, and NE values of a given feed depend on the animal and environmental factors and also measurement and calculation methods. The combination of NE values of diets obtained under standardised conditions allows calculating NE prediction equations that are applicable to both ingredients and compound feeds. The abundance of energy concepts, especially for poultry, and the numerous feed and animal factors of variation related to energy digestibility or ME utilisation for NE suggest that attention must be paid to the experimental conditions for evaluating DE, ME or NE content. This also suggests the necessity of standardisations, one of them being, as implemented in pigs, an adjustment of ME values in poultry for an N retention representative of modern production conditions (MEs). In conclusion, this review illustrates that, in addition to numerous technical difficulties for evaluating energy in pigs and poultry, the absolute energy values depend on feed and animal factors, the environment, and the methods and concepts. Finally, as implemented in pigs, the use of NE values should be the objective of a more reliable energy system for poultry feeds.

PSXII-24 Effects of feeding levels on digestibility, rumen fermentation and blood metabolites of growing Korean native goats (Capra hircus coreanae)

Abstract The objective of this study was to investigate the effects of feeding levels on nutrient digestibility, rumen fermentation and blood metabolites of growing Korean native goats. Five growing bucks (19.5±1.4 kg) with an average age of 5 months were randomly allocated to one of five feeding levels [maintenance (M), 1.1 x M, 1.2 x M, 1.4 x M, and 1.6 x M]. The experimental design was 5 × 5 Latin square design and all animals were housed individual pens (1.2 m × 0.9 m) for an adaption period of 2 weeks and collection period for 1 weeks. Rumen samples were collected before morning feeding using oral stomach tube. Nutrient digestibility increased linearly in goat as feeding level increased (P &amp;lt; 0.01), but body weight did not differ among feeding levels. Rumen pH and ammonia nitrogen concentration showed no significantly differences among feeding levels. The total and individual volatile fatty acids concentration increased linearly (P &amp;lt; 0.01) and quadratically (P &amp;lt; 0.05) with increased feeding levels. Blood metabolites did not differ among feeding levels. The fecal energy loss was not influenced by feeding levels, but digestible energy was increased linearly (P &amp;lt; 0.01) and quadratically (P &amp;lt; 0.05) with increased feeding levels. The metabolizable energy requirement was estimated using quadratic line model and ranged from 154 to 163 kcal per metabolic body weight based on average daily gain and ME intake. These results suggest that higher feeding levels of growing goat increases digestibility and nutrient utilization efficiency in the rumen. These results serve as a basis for the establishment of goat feeding programs at the farm scale in the Republic of Korea.

PSXI-30 Effects of feeding levels on digestibility, rumen fermentation and blood metabolites of fattening Korean native goats (Capra hircus coreanae)

Abstract The objective of this study was to investigate the effects of feeding levels on nutrient digestibility, rumen fermentation and blood metabolites of fattening Korean native goats. Five Korean native goat (Capra hircus coreanae) bucks (38.0±1.7 kg) with an average age of 2.4-year-old were randomly allocated to one of five feeding levels (maintenance [M], 1.1 x M, 1.2 x M, 1.4 x M, and 1.6 x M). The experimental design was 5 × 5 Latin square design and all animals were housed individual pens (1.2 m × 0.9 m) for an adaption period of 2 weeks and collection period for 1 weeks. The average daily gain (P &amp;lt; 0.05) and nutrient digestibility (P &amp;lt; 0.01) were increased linearly in goat as feeding level increased. Rumen pH showed no significantly differences among feeding levels. Total volatile fatty acid, acetate and propionate concentrations were increased linearly (P &amp;lt; 0.01) and quadratically (P &amp;lt; 0.01) with increased feeding levels. Butyrate and ammonia nitrogen concentrations were linearly increased with increased feeding levels (P &amp;lt; 0.01), but valerate concentration did not differ among feeding levels. Blood metabolites did not differ among feeding levels except for albumin concentration which was linearly increased with increased feeding levels (P &amp;lt; 0.05). The fecal energy loss was not influenced by feeding levels, but digestible energy was increased linearly (P &amp;lt; 0.01) and quadratically (P &amp;lt; 0.05) with increased feeding levels. The metabolizable energy requirement was estimated using quadratic line model and ranged from 153 to 161 kcal per metabolic body weight based on average daily gain and ME intake. These results found that the increased feeding level might be improve an average daily gain and ruminal fermentation of Korean native goats in fattening phase. These results may also serve as a basis for the establishment of feeding standard of goats in Republic of Korea.

Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction

Background & AimsEnvironmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.MethodsThe Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.ResultsAfter accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.ConclusionsChildren with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention.ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013)

The Acute Effect of Meal Timing on the Gut Microbiome and the Cardiometabolic Health of the Host: A Crossover Randomized Control Trial

Purpose: The interaction of diet with gut microbiome has been implicated in the onset of cardiovascular disease. The gut microbiome displays diurnal rhythms, which may be influenced by meal timing. Objective: This study aimed to investigate the effect of the timing of main meal consumption on the microbiome and cardiometabolic biomarkers of the host. Methods: Seventeen healthy adults randomly consumed an isocaloric diet for 7 days, twice, by alternating lunch with dinner meals, and with a 2-week washout in-between. Sixty percent of the participants’ daily energy requirements was consumed either as lunch or dinner, respectively. Meals were provided free to the participants. All fecal samples produced the last 3 days of each intervention were collected and analyzed for microbial profiling (16S rRNA gene amplicon sequencing), quantitative estimation of representative bacterial groups (qPCR) of the gut microbiome, and the output of short-chain fatty acids (SCFA) in feces. Fasted blood samples were analyzed for low-grade inflammatory biomarkers, blood lipids, insulin, and glucose levels. Cumulative energy loss in feces was measured over the collection period using bomb calorimetry. Results: Meal timing had no significant effects on fecal SCFA output, energy loss in feces, microbial community profiling, and bacterial species relative abundance. The absolute concentration of Escherichia coli was significantly higher after the large lunch intervention (p = 0.02). No effects on blood biomarkers of cardiometabolic health were observed. Conclusions: In a well-controlled study, main meal timing displayed minimal acute effects on the gut microbiome composition, its diet-related function, and blood biomarkers of cardiometabolic health.

Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.

Obesity is a health problem worldwide, and brown adipose tissue (BAT) is important for energy expenditure. Here, we explored the role of leukotriene A4 hydrolase (LTA4 H), a key enzyme in the synthesis of the lipid mediator leukotriene B4 (LTB4 ), in diet-induced obesity. LTA4 H-deficient (LTA4 H-KO) mice fed a high-fat diet (HFD) showed a lean phenotype, and bone-marrow transplantation studies revealed that LTA4 H-deficiency in non-hematopoietic cells was responsible for this lean phenotype. LTA4 H-KO mice exhibited greater energy expenditure, but similar food intake and fecal energy loss. LTA4 H-KO BAT showed higher expression of thermogenesis-related genes. In addition, the plasma thyroid-stimulating hormone and thyroid hormone concentrations, as well as HFD-induced catecholamine secretion, were higher in LTA4 H-KO mice. In contrast, LTB4 receptor (BLT1)-deficient mice did not show a lean phenotype, implying that the phenotype of LTA4 H-KO mice is independent of the LTB4 /BLT1 axis. These results indicate that LTA4 H mediates the diet-induced obesity by reducing catecholamine and thyroid hormone secretion.

Integrative and quantitative bioenergetics: Design of a study to assess the impact of the gut microbiome on host energy balance

The literature is replete with clinical studies that characterize the structure, diversity, and function of the gut microbiome and correlate the results to different disease states, including obesity. Whether the microbiome has a direct impact on obesity has not been established. To address this gap, we asked whether the gut microbiome and its bioenergetics quantitatively change host energy balance. This paper describes the design of a randomized crossover clinical trial that combines outpatient feeding with precisely controlled metabolic phenotyping in an inpatient metabolic ward. The target population was healthy, weight-stable individuals, age 18–45 and with a body mass index ≤30 kg/m2. Our primary objective was to determine within-participant differences in energy balance after consuming a control Western Diet versus a Microbiome Enhancer Diet intervention specifically designed to optimize the gut microbiome for positive impacts on host energy balance. We assessed the complete energy-balance equation via whole-room calorimetry, quantified energy intake, fecal energy losses, and methane production. We implemented conditions of tight weight stability and balance between metabolizable energy intake and predicted energy expenditure. We explored key factors that modulate the balance between host and microbial nutrient accessibility by measuring enteroendocrine hormone profiles, appetite/satiety, gut transit and gastric emptying. By integrating these clinical measurements with future bioreactor experiments, gut microbial ecology analysis, and mathematical modeling, our goal is to describe initial cause-and-effect mechanisms of gut microbiome metabolism on host energy balance. Our innovative methods will enable subsequent studies on the interacting roles of diet, the gut microbiome, and human physiology. Clinicaltrials.gov identifierNCT02939703. The present study reference can be found here: https://clinicaltrials.gov/ct2/show/NCT02939703.

The effects of the forage-to-concentrate ratio on the conversion of digestible energy to metabolizable energy in growing beef steers.

Metabolizable energy (ME) is calculated from digestible energy (DE) using a constant conversion factor of 0.82. Methane and urine energy losses vary across diets and dry matter intake (DMI), suggesting that a static conversion factor fails to describe the biology. To quantify the effects of the forage-to-concentrate ratio (F:C) on the efficiency of conversion of DE to ME, 10 Angus steers were used in a 5 × 5 replicated Latin square. Dry-rolled corn was included in experimental diets at 0%, 22.5%, 45.0%, 67.5%, and 83.8% on a dry matter (DM) basis, resulting in a high F:C (HF:C), intermediate F:C (IF:C), equal F:C (EF:C), low F:C (LF:C), and a very low F:C (VLF:C), respectively. Each experimental period consisted of a 23-d diet adaption followed by 5 d of total fecal and urine collections and a 24-h gas exchange collection. Contrasts were used to test the linear and quadratic effects of the F:C. There was a tendency (P = 0.06) for DMI to increase linearly as F:C decreased. As a result, gross energy intake (GEI) increased linearly (P = 0.04) as F:C decreased. Fecal energy loss expressed as Mcal/d (P = 0.02) or as a proportion of GEI (P < 0.01) decreased as F:C decreased, such that DE (Mcal/d and Mcal/kg) increased linearly (P < 0.01) as F:C decreased. As a proportion of GEI, urine energy decreased linearly (P = 0.03) as F:C decreased. Methane energy loss as a proportion of GEI responded quadratically (P < 0.01), increasing from HF:C to IF:C then decreasing thereafter. The efficiency of DE to ME conversion increased quadratically (P < 0.01) as F:C decreased, ranging from 0.86 to 0.92. Heat production (Mcal) increased linearly (P < 0.04) as F:C decreased but was not different as a proportion of GEI (P ≥ 0.22). As a proportion of GEI, retained energy responded quadratically (P = 0.03), decreasing from HF:C to IF:C and increasing thereafter. DM, organic matter, and neutral detergent fiber digestibility increased linearly (P < 0.01) and starch digestibility decreased linearly (P < 0.01) as the F:C decreased. Total N retained tended to increase linearly as the proportion of concentrate increased in the diet (P = 0.09). In conclusion, the efficiency of conversion of DE to ME increased with decreasing F:C due to decreasing methane and urine energy loss. The relationship between DE and ME is not static, especially when differing F:C.

Role of Energy Excretion in Human Body Weight Regulation

Food intake and energy expenditure are the typical determinants of body weight. Yet, recent observations underscore that a third and often-neglected factor, fecal energy loss, can influence energy balance. Here, we explore how macronutrient excretion modulates human energy homeostasis and highlight its potential impact on the propensity to gain weight.

Metabolic benefits of gastric bypass surgery in the mouse: The role of fecal losses

ObjectiveRoux-en-Y gastric surgery (RYGB) promotes a rapid and sustained weight loss and amelioration of glucose control in obese patients. A high number of molecular hypotheses were previously tested using duodenal-jejunal bypass (DJB) performed in various genetic models of mice with knockouts for various hormones or receptors. The data were globally negative or inconsistent. Therefore, the mechanisms remained elusive. Intestinal gluconeogenesis is a gut function that has been suggested to contribute to the metabolic benefits of RYGB in obese patients. MethodsWe studied the effects of DJB on body weight and glucose control in obese mice fed a high fat-high sucrose diet. Wild type mice and mice with a genetic suppression of intestinal gluconeogenesis were studied in parallel using glucose- and insulin-tolerance tests. Fecal losses, including excretion of lipids, were studied from the feces recovered in metabolic cages. ResultsDJB induced a dramatic decrease in body weight and improvement in glucose control (glucose- and insulin-tolerance) in obese wild type mice fed a high calorie diet, for 25 days after the surgery. The DJB-induced decrease in food intake was transient and resumed to normal in 7–8 days, suggesting that decreased food intake could not account for the benefits. Total fecal losses were about 5 times and lipid losses 7 times higher in DJB-mice than in control (sham-operated and pair-fed) mice, and could account for the weight loss of mice. The results were comparable in mice with suppression of intestinal gluconeogenesis. There was no effect of DJB on food intake, body weight or fecal loss in lean mice fed a normal chow diet. ConclusionsDJB in obese mice fed a high calorie diet promotes dramatic fecal loss, which could account for the dramatic weight loss and metabolic benefits observed. This could dominate the effects of the mouse genotype/phenotype. Thus, fecal energy loss should be considered as an essential process contributing to the metabolic benefits of DJB in obese mice.

2016-P: High Dose DACRA Treatment Improves Glucose Homeostasis, without Additional Weight Loss

KBP is a Dual Amylin and Calcitonin Receptor Agonist (DACRA). DACRAs have shown efficacy on weight loss and glucose control in rats. However, it is unclear whether the maximum effect has been reached. High Fat Diet (HFD, 60% fat) fed male Sprague-Dawley rats entered a dose escalation regimen ending at 5 (normal dose), 50 or 500 µg/kg daily KBP (n=10/group). Male ZDF (fa/fa) rats received identical doses without dose escalation in a preventive study setup (n=9-10/group). In HFD rats, KBP treatment resulted in a transient decrease in food intake at each dose escalation step. At study end, KBP treatment resulted in a significant weight loss of 77-94 g (13-16%, P&amp;lt;0.0001) compared to vehicle. Furthermore, KBP reduced the weight of adipose tissues (P&amp;lt;0.05). Surprisingly, there was a trend of 5 µg/kg KBP causing a more pronounced adipose-specific weight loss compared to 500 µg/kg (subcutaneous 1.7 vs. 0.7 g, visceral 4.1 vs. 2.5 g adipose weight loss). During two OGTTs, KBP treatment significantly lowered blood glucose (BG) and insulin levels compared to vehicle indicating improved glucose tolerance. Lastly, 24h fecal energy loss increased by KBP treatment, though this trend was absent when accounting for food intake and total feces output. In ZDF rats, KBP treatment significantly improved fasting BG (endpoint vehicle 29.5, endpoint KBP average 18.3 mmol/L, tAUC P&amp;lt;0.0001) and HbA1c (vehicle 10.2%, KBP average 6.1%, P&amp;lt;0.0001) compared to vehicle, with no significant difference between treatment groups. Importantly, fasting and non-fasting insulin levels of KBP-treated rats were increased compared to vehicle in a dose-dependent manner during an OGTT, resulting in lowered BG levels. Increased insulin levels suggest that KBP protects against the known β-cell degradation in the ZDF model. Taken together, these data suggest that higher doses of KBP than previously investigated may preserve insulin secretion to a greater extent. With respect to weight loss, no additional benefit was observed from the high doses. Disclosure N. Sonne: None. A.T. Larsen: None. K.V. Andreassen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Employee; Self; Nordic Bioscience. K. Henriksen: Employee; Self; Nordic Bioscience. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Nordic Bioscience. Other Relationship; Self; Nordic Bioscience.

Novel Long‐Acting GLP‐2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic factor released from L-cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP-2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long-acting GLP-2 analogue, FE 203799 (FE; apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum. Neonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair-fed parenteral and enteral nutrition. Saline and FE (5mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24-hour fecal samples were collected for subsequent nutrient analysis. On day 7, small-intestinal length and weight were measured and tissue collected for analyses. On day 7, saline and FE-treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE-treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small-intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054). The subcutaneous GLP-2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP-2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.

Effects of sea buckthorn pomace supplementation on energy partitioning and substrate oxidation in male lambs

This experiment investigated the effects of dietary sea buckthorn pomace (SBP) supplementation on energy partitioning, substrate oxidation, and carbon and nitrogen balance in ram lambs. A total of 40 1/2 Dorper × 1/2 thin-tailed Han male lambs (BW = 22.2 ± 0.92 kg, Age = 120 ± 11 d; mean ± SD) were randomly selected and equally divided into 4 groups. Diets were formulated isonitrogenously and contained different levels of SBP: 1) 0% SBP (control); 2) 7.8% dry matter (DM) SBP (8SBP); 3) 16.0% DM SBP (16SBP); and 4) 23.5% DM SBP (24SBP). The lambs were fed in individual stalls for 50 d and then determine nutrients digestibility. Gas exchange was then determined using a polycarbonate head box designed for small ruminants. DM and crude protein (CP) intake were greater for 24SBP (2.1 and 0.29 kg/d) than for control (1.28 and 0.24 kg/d) or 8SBP (1.84 and 0.24 kg/d). The treatment diets did not result in difference in metabolisable energy (ME) intake and heat production (HP). Energy and nitrogen loss in feces were higher for lambs fed the 24SBP than for other groups. The nutrient oxidation contribution to the heat production (OXP/HPx, OXCHO/HPx, and OXF/HPx) was not affected by treatment diets (P > 0.228). The highest values of retention of energy in fat (REfat) and total tissue (REtotal) were observed in 16SBP diet. The results indicated that sea buckthorn pomace can be incorporated in the diet of ram lambs, and inclusion of 16% SBP in the diet had no detrimental effect on energy metabolism and resulted in an increase in energy retention.

Energy partition, nutritional energy requirements and methane production in F1 Holstein × Gyr bulls, using the respirometric technique

The nutritional energy requirements of animals for maintenance and weight gain, such as the energy partition of the diet, were determined in different feeding plans. Fifteen F1 Holstein × Gyr, non-castrated male bovines with a mean initial liveweight of 302 kg were used. The diets were corn silage and concentrate, formulated to enable gains of 100, 500 and 900 g/day, called low, medium and high weight gains, respectively. Tests of digestibility and metabolism were conducted to determine energy losses through faeces, urine and methane emissions. Heat production was determined using respirometry chamber. Net energy for maintenance was calculated as the antilogarithm of the intercept of the regression of the logarithm of the heat production, as a function of the metabolisable energy intake. Retained energy was obtained by subtracting the heat production from the metabolisable energy intake. With the increased consumption of dry matter, there was an increase in faecal and urinary energy loss. Retained energy increased linearly with the metabolisable energy intake. The net energy for gain in the diet did not differ among the treatments, such as the efficiency of use of metabolisable energy for weight gain kg (0.34). The net energy for maintenance was 312 kJ/kg LW0.75, and the metabolisable energy for maintenance was 523 kJ/kg LW0.75. The daily methane production (g/day) increased with the dry matter level and the daily loss represented 5.31% of the gross energy consumption.