Equal Weight Gain Research Articles

Partial Replacement of Fishmeal with Duckweed (Spirodela polyrhiza) in Feed for Two Carnivorous Fish Species, Eurasian Perch (Perca fluviatilis) and Rainbow Trout (Oncorhynchus mykiss)

Two four-week feeding trials were conducted with fingerlings of Eurasian perch (Perca fluviatilis, 3.52 ± 0.08 g) and rainbow trout (Oncorhynchus mykiss, 1.49 ± 0.05 g) fed with graded levels of dried (DWD) and fermented (DWF) duckweed meal (Spirodela polyrhiza). The purpose of these two trials was to evaluate DWD and DWF as replacements for fishmeal. Fishmeal protein was substituted by 12%, 24%, and 35% of duckweed protein and compared to control diets containing 40% (for perch) and 35% (for rainbow trout) fishmeal and no duckweed. The performance of the fish (growth, feed conversion, and protein and lipid utilization) and their whole-body composition were evaluated and compared with the control. While even the lowest inclusion level, regardless of its form (dried or fermented), resulted in significantly reduced performance in Eurasian perch, rainbow trout were able to utilize feed containing duckweed meal considerably well. Compared to the control, at a 12% inclusion level, rainbow trout showed an equal or comparable percent weight gain (PWG; DWD: 377%, DWF: 373%), specific growth rate (SGR; DWD: 4.37%/day, DWF: 4.33%/day), feed conversion ratio (FCR; DWD: 1.11, DWF: 1.12), and protein productive value (PPV; DWD: 21.5%, DWF: 21.2%). Increasing the inclusion levels above 12% of both DWD and DWF resulted in reduced performance in rainbow trout, with the most pronounced effects observed in the DWD35 group. All experimental diets, including control, affected the whole body composition of perch, most notably reducing the lipid content compared to initial fish. Compared to initial, control and DWD rainbow trout increased whole-body protein, lipid, and ash contents. In conclusion, for rainbow trout, fermented and dried S. polyrhiza duckweed meal appears to be a promising feed ingredient when used at a maximum inclusion level of 12%, while for Eurasian perch, it should not be considered as a feed ingredient.

Complete replacement of fish oil and fish meal in the diet of juvenile California yellowtail Seriola dorsalis

California yellowtail (CYT) Seriola dorsalis is a top candidate for aquaculture in southern California. CYT is fed commercial diets whose nutrient profile and ingredient composition rely heavily on fish meal and fish oil. We evaluated the complete replacement of fish oil and fish meal with a Schizochytrium-derived algal oil as an essential fatty acid source and poultry by-product meal and spirulina as primary protein sources, in the diet of juvenile CYT (average initial weight—19.95 ± 0.09 g). The treatment diets for this study included the following: FMF-FO—fish meal free, fish oil; FMF-AO—fish meal free, algal oil; FMF-SO—fish meal free, soybean oil; FMC-FO—fish meal control, fish oil. Each treatment diet was formulated to contain 45% protein and 15% lipid, and the trial lasted 64 days. At the conclusion of the trial, fish from FMC-FO group had performed significantly better in three key performance metrics: final body weight of 185.96 ± 8.98 g, per cent weight gain of 832.7 ± 47.2% and lowest FCR of 1.16 ± 0.04. Replacing fish meal with poultry by-product meal and spirulina resulted in 20% less weight gain. Replacing fish oil with algal oil, in a fish meal free diet, resulted in equal weight gain, and the fish had higher tissue essential fatty acid content. Based on the results from this trial, we have shown that in CYT juvenile diets, fish oil can be replaced with algal oil with no effect on growth or survival and fish meal can be replaced with no effect on survival and a 20% decrease in weight gain.

Effects of exchanging lactose for fat in milk replacer on ad libitum feed intake and growth performance in dairy calves

The recent trend in the dairy industry toward ad libitum feeding of young calves merits reconsideration of calf milk replacer (CMR) formulations. Additionally, feed intake regulation in young calves provided with ad libitum milk and solid feeds is insufficiently understood. This study was designed to determine the effect of exchanging lactose for fat in CMR on voluntary feed intake and growth performance. Lactose was exchanged for fat on a weight/weight basis, resulting in different energy contents per kilogram of CMR. Thirty-two male calves (1.7 ± 0.12 d of age, 47.6 ± 0.83 kg of body weight) were assigned to 1 of 16 blocks based on arrival date. Within each block, calves were randomly assigned to 1 of 2 treatments. The experimental period was divided into 4 periods. In period 1, until 14 ± 1.7 d of age, calves were individually housed, restricted-fed their assigned CMR treatments at 2.5 to 3 L twice daily, and provided with unlimited access to water, chopped straw, and starter. In period 2, calves were group-housed with 8 calves per pen and received ad libitum access to their assigned CMR treatments, starter feed, chopped wheat straw, and water. During period 3, from 43 until 63 d of age, calves were weaned by restricting CMR allowance in 2 steps, maintaining access to all other feeds. All calves were completely weaned at d 64 of age and were monitored until 77 d of age (period 4). Measurements included the intake of all dietary components, body weight gain, and a selection of blood traits. Increasing fat content at the expense of lactose decreased CMR intake by 10%, whereas total calculated metabolizable energy intake and growth remained equal between treatments. Total solid feed (starter and straw) consumption was not affected by CMR composition. These data indicate that calves fed ad libitum regulate their CMR intake based on energy content. High-fat CMR increased plasma phosphate, nonesterified fatty acids, triglycerides, and bilirubin, whereas plasma glucose remained unchanged. Despite the limited animal numbers in the present experiment, there was a significant decrease in the total number of health events (mainly respiratory) requiring therapeutic intervention and in the total number of therapeutic interventions in calves fed high-fat CMR. Calves appeared to consume CMR based on energy content, with a difference in ad libitum intake proportional to the difference in energy content of the CMR, maintaining equal body weight gain and solid feed intake.

Baker's yeast (1→3)-β-D-glucan Influences Insulin Sensitivity in Mice with Humanized Obese Diabetic Microbiome in High-Fat Diet-Induced Obesity

AbstractIntroductionβ-glucans are naturally occurring polysaccharides which have isoform specific immunomodulatory and metabolic properties(1). Certain yeast (1→3)-β-D-glucan isoforms improve cholesterol(2), glucose(3) and lipid homeostasis(4). Feeding (1→3)-β-D-glucan alters the microbiome of high-fat diet (HFD) induced obese (DIO)/type 2 diabetic (T2D) mice(5). Here we investigated the potential impact of baker's yeast (1→3)-β-D-glucan in mice humanized with gut microbiomes from either obese healthy versus obese diabetic subjects on immune-metabolism within the context of high-fat feeding.MethodsC57Bl/6J male mice received an antibiotic cocktail of Ampicillin, Metronidazole, Vancomycin, Imipenem and Ciprofloxacin HCl in their drinking water for 6 weeks to diminish the endogenous gut microbiota. Mice were inoculated with microbiota samples obtained from obese healthy (OBH) or diabetic (OBD) humans twice daily for 3 days by oral dosing. Mice were fed a low-fat diet (LFD) (10% kcal) for 4 weeks followed by HFD (45% kcal) with/without baker's yeast (1→3)-β-D-glucan (βG), for 9 weeks. Weight, feed intake, glucose tolerance (1.5g/kg), insulin tolerance (0.5U/kg), hepatic and skeletal lipid levels were examined. Tissue specific molecular markers of metabolism and inflammation, and gut microbiome analysis are being determined to compliment the phenotypic data.ResultsOBH mice were more glucose tolerant and insulin sensitive than OBD mice, despite equal weight gain and adipose tissue mass. Fasting HOMA-IR, attributable to higher insulin concentrations, was higher in OBD compared to OBH mice. βG supplementation reduced HOMA-IR in OBD mice (P < 0.0611). Hepatic triacylglycerol (TAG) and cholesterol levels were also higher in OBD mice, which were prevented by βG supplementation. Hepatic proteomic, caecal microbiomic and metabolomic analysis is on-going in order to ascertain the impact of the OBD versus OBH dysbosis with/without βG supplementation with specific attention on immune-metabolism.

Effect of Napier Grass on Economic Turkey Production in Bangladesh

Objective: To test the hypothesis that a certain percent of Napier grass could be used as a replacement of concentrate for economic production of turkey. Method/Analysis: The feeding trial was a Completely Randomized Design (CRD) consisting of one control and two concentrate feed replacement treatments. Three treatments were: T1 = 100% concentrate (control), T2 = 75% concentrate + 25% grass and T3 = 50% concentrate + 50% grass. Requirement of concentrate and Napier grass were determined and supplied on the basis of Dry Matter (DM). Turkeys of all treatments were fed with the feed of same composition. Findings: Significant (P<0.05) difference was observed in daily and weekly concentrate intake among the treatment groups. Napier grass intake also differed significantly (P<0.05). Similar final body weight was found in T1 (2006 ± 102.5 g) and T2 (2008 ± 77.5 g). Feed conversion efficiency was better (P<0.05) for T2 (2.54 ± .01) and T3 (2.63 ± 0.05) than T1 (3.50 ± 0.05). Survivability rate was higher (P<0.05) in T2 (100%) and T3 (100%) than T1 (93%). Production cost and profitability per turkey differed significantly (P<0.05). Although total revenue was similar in T1 and T2 ; net farm income, production index, rate of return on investment and capital turnover were significantly (P<0.05) higher in T2 . Novelty: Finally, it was concluded that on the basis of DM, replacement of 25% concentrate by Napier grass resulted in not only equal weight gain as like 100% concentrate but also reduced cost of production without causing any detrimental effects on turkey aged between 5 to 14 weeks. Therefore, farmers of Bangladesh could use this feeding system for economic turkey production. Keywords: Concentrate, Feed Efficiency, Growth, Napier Grass, Turkey+

Responsiveness of swine divergently selected for feed efficiency to exogenous adrenocorticotropic hormone and glucose challenges

Increasing the feed efficiency of lean tissue gains is an important goal for improving sustainable pork production and profitability for swine producers. To study feed efficiency, genetic selection based on residual feed intake (RFI) was used to create two divergent lines. Low-RFI pigs consume less feed for equal weight gain compared with their less-efficient, high-RFI counterparts. As cortisol and insulin are important energy control and growth regulators, our objective was to evaluate the role of the adrenocorticotropic hormone (ACTH)-cortisol and the glucose-insulin axes in pigs divergently selected for RFI. Adrenocorticotropic hormone (0.2 IU/kg BW)–stimulated cortisol and non-esterified fatty acids (NEFA) concentrations and intravenous glucose tolerance test (IVGTT; 0.25 g/kg BW)–stimulated glucose, insulin, and NEFA concentrations were assessed in six low-RFI and six high-RFI gilts (68 ± 5.2 kg). Before the ACTH challenge, low-RFI gilts tended to have less baseline plasma cortisol (P = 0.08) but no difference in NEFA concentrations (P = 0.63) compared with high-RFI gilts. After the ACTH challenge, low-RFI gilts had less cortisol (P = 0.04) and NEFA concentrations (P = 0.05) compared with high-RFI gilts. Glucose, insulin, and NEFA concentrations did not differ between genetic lines before the IVGTT. After glucose infusion, low-RFI gilts had greater insulin concentrations (P = 0.003) but did not differ in glucose or NEFA concentrations compared with high-RFI gilts. These results indicate that genetic selection for reduced RFI (improved feed efficiency) resulted in less stress responsiveness and an increase in insulin after glucose infusion. These data have implications for identifying and selecting more feed efficient pigs and for understanding the physiological mechanisms underlying feed efficiency.

Effect of Aging and High Fat Diet on Mitochondrial and Cardiac Function in Mice with Altered Mitochondrial DNA Repair

In the developing heart it is important that mitochondrial biogenesis is precisely coordinated with cardiac growth, because impaired bioenergetic function could lead to heart failure. Oxidative mitochondrial (mt) DNA damage and repair play critical roles in mitochondrial biogenesis during postnatal cardiac development in rodents; therefore heart development could be adversely impacted by alterations in mtDNA repair. Our previous results showed that young mice deficient in the DNA repair glycosylase Ogg1, the first enzyme in the base excision repair pathway in mitochondria, displayed increased mtDNA damage, altered mitochondrial respiration and left ventricle hypertrophy. Surprisingly, despite these abnormalities, cardiac function in 3 week old Ogg1‐deficient animals remained unchanged. However, whether these cardiac compensatory mechanisms remain effective during aging or under stress conditions is unclear. Here we test the hypothesis that increased oxidative stress associated with aging and obesity decreases cardiac function and leads to development of cardiomyopathy in mice with altered mitochondrial DNA repair. Fifteen month old mice of three genotypes ‐ wild type (WT), Ogg1 knock‐out (KO) animals and KO mice transgenically overexpressing mitochondria‐targeted Ogg1 (KOTG) were fed a high fat diet for 14 weeks and analyzed for mtDNA damage and copy number, mitochondrial respiration, and for cardiac function. Despite approximately equal weight gain in all three groups of animals, mitochondrial and cardiac function characteristics were different for these genotypes. Compared to WT, KO mice displayed increased oxidative mtDNA damage and decreased mtDNA copy number in cardiac tissue. Conversely, mtDNA oxidation was decreased and mtDNA copy number restored in KOTG mice. Echocardiographic analysis demonstrated increased left ventricle mass and decreased cardiac contractility in KO mice. Compared to hearts from WT mice, KO animals displayed a significant increase in mitochondrial oxygen flux at state III that remained elevated after adding an uncoupling agent. Taking into account decreases in respiratory ratio and abnormally low ATP levels in KO mice, these results indicate that there is constitutive uncoupling in the cardiac tissue of Ogg1 deficient animals. These changes in cardiac function and mitochondrial bioenergetics observed in KO mice were prevented in KOTG mice, which were not different from WT animals. In summary, oxidative stress associated with aging and obesity lead to elevated oxidative mtDNA damage, decreased mtDNA copy number, mitochondrial dysfunction, and impaired cardiac contractility in Ogg1 deficient mice. Restoration of mtDNA repair in KOTG animals eliminated these effects on mitochondrial and cardiac function, thus demonstrating an important role of mtDNA integrity in maintenance of mitochondrial and cardiac health. Further, these results suggest that abnormalities in mitochondrial and cardiac function can be manipulated by altering mtDNA damage and repair.Support or Funding InformationSupported by NIH.

A Prebiotic Blend of Polydextrose and Galactooligosaccharides with Bioactive Whey Protein Fractions Ameliorates Stress‐evoked Disruptions in Sleep States

Stressor exposure can produce disruptions in sleep that may contribute to altered behavioral phenotypes. Prebiotics can selectively promote the expansion of microbial species in the mammalian gut that may increase stress robustness. Previous studies showed that a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) increase Bifidobacterium spp. and Lactobacillus spp. in fecal samples. In this study, we hypothesized that an experimental diet would modulate the sleep cycle and protect sleep architecture following stress. Male F344 rats, postnatal day 24 (P24), were placed on either a diet containing a prebiotic blend of PDX and GOS with bioactive whey protein fractions (TEST) or a control diet. Fecal samples were collected and telemetry devices were implanted to examine differences in sleep across development. Rats were exposed to an acute stressor on P87 to examine the effects of the TEST diet on stress-induced disruptions of sleep. Rats fed the TEST diet, when compared with rats fed the control diet, had equal weight gain and greater NREM sleep consolidation in early adulthood. Rats fed the TEST diet also displayed enhanced REM rebound after stress. These results demonstrate that the selected dietary factors can increase NREM sleep consolidation and protect against REM sleep disruptions. Future research will examine if other functional outcomes, such as cognitive processes, may be associated with these changes in sleep parameters.

Feed efficiency effects on barrow and gilt behavioral reactivity to novel stimuli tests.

Increasing feed efficiency is an important goal for improving sustainable pork production and profitability for producers. To study feed efficiency, genetic selection based on residual feed intake (RFI) was used to create 2 divergent lines. Low-RFI pigs consume less feed for equal weight gain compared to their less efficient, high-RFI counterparts. Therefore, our objective was to assess how a pig's behavioral reactivity toward fear-eliciting stimuli related to RFI selection and improvement of feed efficiency. In this study, behavioral reactivity of pigs divergently selected for RFI was evaluated using human approach (HAT) and novel object (NOT) tests. Forty low-RFI and 40 high-RFI barrows and gilts ( = 20 for each genetic line; 101 ± 9 d old) from ninth-generation Yorkshire RFI selection lines were randomly selected and evaluated once using HAT and once using NOT over a 2-wk period utilizing a crossover experimental design. Each pig was individually tested within a 4.9 × 2.4 m test arena for 10 min; behavior was evaluated using live and video observations. The test arena floor was divided into 4 zones; zone 1 being oral, nasal, and/or facial contact with the human (HAT) or orange traffic cone (NOT) and zone 4 being furthest from the human or cone and included the point where the pig entered the arena. During both HAT and NOT, low-RFI pigs entered zone 1 less frequently compared to high-RFI pigs ( ≤ 0.03). During NOT, low-RFI pigs changed head orientation more frequently ( = 0.001) but attempted to escape less frequently (low-RFI = 0.97 ± 0.21 vs. high-RFI = 2.08 ± 0.38; = 0.0002) and spent 2% less time attempting to escape compared to high-RFI pigs ( = 0.04). Different barrow and gilt responses were observed during HAT and NOT. During HAT, barrows spent 2% more time within zone 1 ( = 0.03), crossed fewer zone lines ( < 0.0001), changed head orientation less frequently ( = 0.002), and froze less frequently compared to gilts ( = 0.02). However, during NOT, barrows froze more frequently ( = 0.0007) and spent 2% longer freezing ( = 0.05). When the behavior and RFI relationship was examined using odds ratios, decreasing RFI by 1 kg/d decreased the odds of freezing by 4 times but increased the odds of attempting to escape by 5.26 times during NOT ( ≤ 0.04). These results suggest that divergent selection for RFI resulted in subtle behavioral reactivity differences and did not impact swine welfare with respect to responses to fear-eliciting stimuli.

Effects of genetic selection for residual feed intake on behavioral reactivity of castrated male pigs to novel stimuli tests

Increasing feed efficiency in swine is important for increasing sustainable food production and profitability for producers; therefore, this is often selected for at breeding. Residual feed intake (RFI) can be used for the genetic selection of pigs for feed efficiency. In our selection project, low-RFI pigs consume less feed for equal weight gain compared to their less efficient, high-RFI counterparts. However, little is known about how feed efficiency influences the pig's behavioral reactivity toward fear-eliciting stimuli. In this study, behavioral reactivity of pigs divergently selected for RFI was evaluated using human approach- (HAT) and novel object tests (NOT). Forty low-RFI (more feed efficient) and 40 high-RFI (less feed efficient) castrated male pigs (barrows; 46.5±8.6kg) from 8th generation Yorkshire RFI selection lines were randomly selected and evaluated once using HAT and once using NOT over a four week period utilizing a crossover experimental design. Each pig was individually tested within a 4.9×2.4m test arena for 10min; behavior was evaluated using live and video observations. The test arena floor was divided into four zones; zone 1 being oral, nasal, and/or facial contact with the human (HAT) or orange traffic cone (NOT) and zone 4 being furthest from the human or cone and included the point where the pig entered the arena. During both HAT and NOT, low-RFI pigs crossed fewer zones (P<0.0001), had fewer head movements (P≤0.02), defecated less frequently (P≤0.03), displayed a shorter duration of freezing (P=0.05), and froze less frequently (HAT: low-RFI=4.9±0.65 vs. high-RFI=7.5±0.96; NOT: low-RFI=4.7±0.66 vs. high-RFI=7.2±0.96; P<0.0001) compared to high-RFI pigs. During HAT, low-RFI pigs also attempted to escape less frequently (low-RFI=0.4±0.14 vs. high-RFI=1.1±0.30; P=0.001) compared to high-RFI pigs. In contrast, compared to the high-RFI pigs, low-RFI pigs took 48s longer during HAT and 52s longer during NOT to approach zone 1 (P≤0.04). These results indicate that low-RFI pigs had decreased behavioral reactivity during HAT and NOT compared to high-RFI pigs. This may suggest that reducing a pig's behavioral reactivity is an important component of improving feed efficiency; however, it may have implications for animal handling and facility design.

Effects of Methyl Donor Diets on Incisional Pain in Mice

BackgroundDietary supplementation with methyl donors can influence the programming of epigenetic patterns resulting in persistent alterations in disease susceptibility and behavior. However, the dietary effects of methyl donors on pain have not been explored. In this study, we evaluated the effects of dietary methyl donor content on pain responses in mice.MethodsMale and female C57BL/6J mice were treated with high or low methyl donor diets either in the perinatal period or after weaning. Mechanical and thermal nociceptive sensitivity were measured before and after incision.ResultsMice fed high or low methyl donor diets displayed equal weight gain over the course of the experiments. When exposed to these dietary manipulations in the perinatal period, only male offspring of dams fed a high methyl donor diet displayed increased mechanical allodynia. Hindpaw incision in these animals caused enhanced nociceptive sensitization, but dietary history did not affect the duration of sensitization. For mice exposed to high or low methyl donor diets after weaning, no significant differences were observed in mechanical or thermal nociceptive sensitivity either at baseline or in response to hindpaw incision.ConclusionsPerinatal dietary factors such as methyl donor content may impact pain experiences in later life. These effects, however, may be specific to sex and pain modality.

Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that reducing excess maternal inflammation may be a promising target for preventing adverse fetal metabolic outcomes in pregnancies complicated by maternal obesity.

Dietary methyl content regulates opioid responses in mice

BackgroundLarge interindividual differences in clinical responses to opioids and the variable susceptibility to abuse of this class of drugs make their use problematic. We lack a full understanding of the factors responsible for these differences. Dietary factors including methyl donor content have been noted to alter multiple physiological and behavioral characteristics of laboratory animals. The purpose of this research was to determine the effects of dietary methyl donor content on opioid responses in mice.MethodsGroups of male C57BL/6J mice were treated with high and low methyl donor diets either in the perinatal period or after weaning. Analgesic responses to morphine, as well as tolerance, opioid-induced hyperalgesia, and physical dependence were assessed.ResultsMice fed high and low methyl donor diets showed equal weight gain over the course of the experiments. Exposure to a high methyl donor diet in the perinatal period enhanced physical dependence. Dietary methyl donor content also altered analgesic responses to low doses of morphine when the dietary treatments were given to the mice after weaning. Opioid-induced hyperalgesia was unaltered by dietary methyl donor content.ConclusionHigh and low methyl donor diet treatment has selective effects on opioid responses depending on the timing of exposure. These findings suggest that examination of DNA methylation patterns in specific brain regions linked to opioid analgesia and dependence may provide specific explanations for dietary effects on opioid responses.

Inter‐organ proteomic analysis reveals insights into the molecular mechanisms underlying the anti‐diabetic effects of cis‐9, trans‐11‐conjugated linoleic acid in ob/ob mice

cis-9, trans-11-Conjugated linoleic acid (c9 t11 CLA) exerts anti-diabetic effects by improving systemic insulin sensitivity and inflammation. Levels of CLA in beef can be increased by feeding cattle on pasture. This study aimed to explore the efficacy of a CLA-rich diet (0.6% w/w c9 t11 CLA), presented as beef enriched with CLA or beef supplemented with synthetic CLA (c9 t11 CLA), for 28 days on molecular biomarkers of the metabolic syndrome, and adipose, hepatic, and skeletal muscle proteome in male ob/ob mice. Despite equal weight gain, CLA-fed mice had lower plasma glucose, insulin, non-esterified fatty acid, triacylglycerol and interleukin-6, and higher adiponectin concentrations than controls. c9 t11 CLA induced differential regulation of redox status across all tissues, and decreased hepatic and muscle endoplasmic reticulum stress. CLA also modulated mechanistic links between the actin cytoskeleton, insulin signalling, glucose transport and inflammation in the adipose tissue. In the liver and muscle, c9 t11 CLA improved metabolic flexibility through co-ordination between carbohydrate and energy metabolism. c9 t11 CLA may ameliorate systemic insulin sensitivity in obesity-induced diabetes by altering cellular stress and redox status, and modulating nutrient handling in key insulin-sensitive tissues through complex biochemical interplay among representative proteomic signatures.

Weight Cycling and Cancer: Weighing the Evidence of Intermittent Caloric Restriction and Cancer Risk

Overweight and obese individuals frequently restrict caloric intake to lose weight. The resultant weight loss, however, typically is followed by an equal or greater weight gain, a phenomenon called weight cycling. Most attention to weight cycling has focused on identifying its detrimental effects, but preclinical experiments indicating that intermittent caloric restriction or fasting can reduce cancer risk have raised interest in potential benefits of weight cycling. Although hypothesized adverse effects of weight cycling on energy metabolism remain largely unsubstantiated, there is also a lack of epidemiologic evidence that intentional weight loss followed by regain of weight affects chronic-disease risk. In the limited studies of weight cycling and cancer, no independent effect on postmenopausal breast cancer but a modest enhancement of risk for renal cell carcinoma, endometrial cancer, and non-Hodgkin's lymphoma have been reported. An effect of either intermittent caloric restriction or fasting in protecting against cancer is not supported by the majority of rodent carcinogenesis experiments. Collectively, the data argue against weight cycling and indicate that the objective of energy balance-based approaches to reduce cancer risk should be to strive to prevent adult weight gain and maintain body weight within the normal range defined by body mass index.

Monoglyceride Lipase Deficiency in Mice Impairs Lipolysis and Attenuates Diet-induced Insulin Resistance

Monoglyceride lipase (MGL) influences energy metabolism by at least two mechanisms. First, it hydrolyzes monoacylglycerols (MG) into fatty acids and glycerol. These products can be used for energy production or synthetic reactions. Second, MGL degrades 2-arachidonoyl glycerol (2-AG), the most abundant endogenous ligand of cannabinoid receptors (CBR). Activation of CBR affects energy homeostasis by central orexigenic stimuli, by promoting lipid storage, and by reducing energy expenditure. To characterize the metabolic role of MGL in vivo, we generated an MGL-deficient mouse model (MGL-ko). These mice exhibit a reduction in MG hydrolase activity and a concomitant increase in MG levels in adipose tissue, brain, and liver. In adipose tissue, the lack of MGL activity is partially compensated by hormone-sensitive lipase. Nonetheless, fasted MGL-ko mice exhibit reduced plasma glycerol and triacylglycerol, as well as liver triacylglycerol levels indicative for impaired lipolysis. Despite a strong elevation of 2-AG levels, MGL-ko mice exhibit normal food intake, fat mass, and energy expenditure. Yet mice lacking MGL show a pharmacological tolerance to the CBR agonist CP 55,940 suggesting that the elevated 2-AG levels are functionally antagonized by desensitization of CBR. Interestingly, however, MGL-ko mice receiving a high fat diet exhibit significantly improved glucose tolerance and insulin sensitivity in comparison with wild-type controls despite equal weight gain. In conclusion, our observations implicate that MGL deficiency impairs lipolysis and attenuates diet-induced insulin resistance. Defective degradation of 2-AG does not provoke cannabinoid-like effects on feeding behavior, lipid storage, and energy expenditure, which may be explained by desensitization of CBR.

E IGFBP-1 upregulates vascular nitric oxide via PI-3-K activation and rescues endothelial function in murine models of insulin resistance: Abstract E Table 1

<h3>Background</h3> Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) predict the development of diabetes and cardiovascular disease. Whether IGFBP-1 has direct influences on the vasculature remains unknown however. We previously showed that transgenic over-expression of IGFBP-1 in lean mice conferred favourable effects on endothelial function and blood pressure. We now present data demonstrating that IGFBP-1 increases nitric oxide (NO) production in endothelial cells via PI-3-K activation, and protects against the cardiovascular consequences of insulin resistance in mice. <h3>Methods</h3> Male IGFBP-1 transgenic C57Bl/6 mice and littermate controls were challenged by two models of insulin resistance: (i) diet-induced obesity (DIO) and; (ii) crossing with heterozygous insulin receptor knockout mice (IRKO). Cardiovascular function was assessed by tail cuff blood pressure, aortic ser¹¹⁷⁷eNOS phosphorylation following in vivo insulin bolus, and aortic vasomotion ex vivo. Metabolic function was also assessed in DIO mice by insulin- and glucose-tolerance testing, and skeletal muscle Akt⁴⁷³ phosphorylation following in vivo insulin bolus. To dissect the mechanisms by which IGFBP-1 modulates endothelial function, complementary in vitro studies were conducted with exogenous IGFBP-1. Thus, after incubation with IGFBP-1, we tested vasomotion in intact aorta (organbath), NO generation in HUVECs (citrulline assay) and ser¹¹⁷⁷eNOS phosphorylation in HUVECs (western blot and immunofluorescence). Upstream signalling pathways were further probed using targeted signalling inhibitors. <h3>Results</h3> Both DIO and IRKO mice predictably developed endothelial dysfunction and hypertension. In contrast, IGFBP-1 transgenic mice with DIO or IRKO had preserved endothelial function, normal blood pressure, and improved gluco-regulation in DIO despite equal weight gain (see Abstract E table 1). In HUVECs and intact aorta, IGFBP-1 induced dose- and time-dependent ser¹¹⁷⁷ phosphorylation of eNOS and NO generation via PI-3-K activation. No IGF-I was present in these in vitro assays and these findings were reproducible in vessels with homozygous knockout of the endothelial IGF-receptor, indicating that the actions of IGFBP-1 on the vasculature are independent of IGF-I. <h3>Implications</h3> IGFBP-1 improves endothelial function independently of IGF-I and protects against the cardiovascular and metabolic consequences of insulin resistance. Restoration of IGFBP-1 levels may thus be a novel therapeutic target to mitigate cardiovascular risk.

Attenuation of inflammation and cellular stress‐related pathways maintains insulin sensitivity in obese type I interleukin‐1 receptor knockout mice on a high‐fat diet

The development of insulin resistance in the obese is associated with chronic, low-grade inflammation. We aimed to identify novel links between obesity, insulin resistance and the inflammatory response by comparing C57BL/6 with type I interleukin-1 receptor knockout (IL-1RI(-/-)) mice, which are protected against diet-induced insulin resistance. Mice were fed a high-fat diet for 16 wk. Insulin sensitivity was measured and proteomic analysis was performed on adipose, hepatic and skeletal muscle tissues. Despite an equal weight gain, IL-1RI(-/-) mice had lower plasma glucose, insulin and triacylglycerol concentrations, compared with controls, following dietary treatment. The higher insulin sensitivity in IL-1RI(-/-) mice was associated with down-regulation of antioxidant proteins and proteasomes in adipose tissue and hepatic soluble epoxide hydrolase, consistent with a compromised inflammatory response as well as increased glycolysis and decreased fatty acid beta-oxidation in their muscle. Their lower hepatic triacylglycerol concentrations may reflect decreased flux of free fatty acids to the liver, decreased hepatic fatty acid-binding protein expression and decreased lipogenesis. Correlation analysis revealed down-regulation of classical biomarkers of ER stress in their adipose tissue, suggesting that disruption of the IL-1RI-mediated inflammatory response may attenuate cellular stress, which was associated with significant protection from diet-induced insulin resistance, independent of obesity.

Replacement of fish meal in cobia (Rachycentron canadum) diets using an organically certified protein

A six-week feeding trial was conducted to evaluate the use of a yeast-based, certified organic protein source as a replacement for fish meal in diets for cobia. Five experimental diets were formulated to provide 40% crude protein and 11% dietary lipid (dry matter basis) with the yeast-based protein source replacing Special Select® menhaden fish meal at 25%, 50%, 75% and 100% of dietary protein. Ten juvenile cobia (initial weight 11.5 g/fish) were randomly stocked in triplicate 300 l circular fiberglass tanks (n=30 treatment−1) and hand-fed the diets based upon total tank biomass two times daily at 0900 and 1400 h. Fish were group weighed weekly to monitor performance and adjust feeding rations. Water temperature and salinity were maintained at 27 °C and 15‰, respectively.At the end of the feeding trial, weight gain, ranging from 86% to 512%, and feed conversion ratio values, ranging from 1.9 to 5.8, were significantly affected by the inclusion of the yeast-based protein source, with decreasing values as inclusion levels of the yeast-based protein source rose above 25% of dietary protein. Cobia fed the diet containing 25% of dietary protein from the yeast-based protein source had equal weight gain and feed conversion ratio values as fish fed the control diet composed of 100% fish meal (503 vs. 512 and 1.9 vs. 1.9, respectively). Biological indices including hepatosomatic index, visceral somatic index and muscle ratio were all similarly affected by inclusion of the yeast-based protein source, with significant impacts when inclusion levels rose above 25% of dietary protein. As with the weight gain and feed efficiency ratio values, fish fed the diet containing 25% of protein from the yeast-based source had similar values as those observed in the control animals.This study represents the first attempt to utilize an organically certified protein source as a replacement for fish meal in diets for juvenile cobia. Although levels of inclusion of the yeast-based protein source above 50% of dietary protein resulted in detrimental effects on production characteristics, the data clearly suggest that, at a minimum, 25% of dietary protein can be provided by this yeast-based protein in diets for cobia.

Supplements of transgenic malt or grain containing (1,3-1,4)-ß-glucanase increase the nutritive value of barley-based broiler diets to that of maize

1. A diet with addition to normal barley of malt from transgenic barley expressing a protein engineered, thermotolerant Bacillus (1,3-1,4)-β-glucanase during germination has previously been demonstrated to provide a broiler chicken weight gain comparable to maize diets. It also reduced dramatically the number of birds with adhering sticky droppings, but did not entirely eliminate sticky droppings. One of the objectives of the broiler chicken trials reported here was to determine if higher concentrations of transgenic malt could alleviate the sticky droppings. 2. Another aim was to investigate the feasibility of using mature transgenic grain containing the thermotolerant (1,3-1,4)-β-glucanase as feed addition and to compare diets containing transgenic grain to a diet with the recommended amount of a commercial β-glucanase-based product. 3. Inclusion of 75 or 151 g/kg transgenic malt containing 4·7 or 98 mg/kg thermotolerant (1,3-1,4)-β-glucanase with 545 or 469 g/kg non-transgenic barley instead of maize yielded a weight gain in Cornish Cross broiler chickens indistinguishable from presently used maize diets. The gene encoding the enzyme is expressed in the aleurone with a barley α-amylase gene promoter and the enzyme is synthesised with a signal peptide for secretion into the endosperm of the malting grain. 4. Equal weight gain was achieved, when the feed included 39 g/kg transgenic barley grain [containing 66 mg/kg thermotolerant (1,3-1,4)-β-glucanase] and 581 g/kg non-transgenic barley instead of maize. In this case, the gene encoding the enzyme has been expressed with the D-hordein gene (Hor3-1) promoter during grain maturation. The enzyme is synthesised as a precursor with a signal peptide for transport through the endoplasmic reticulum and targeted into the storage vacuoles. Deposition of the enzyme in the prolamin storage protein bodies of the endosperm protects it from degradation during the programmed cell death of the endosperm in the final stages of grain maturation and provides extraordinary heat stability. The large amount of highly active (1,3-1,4)-β-glucanase in the mature grain allowed the reduction of the transgenic grain ingredient to 0·2 g/kg diet, thus making the ingredient comparable to that of the trace minerals added to standard diets. 5. A direct comparison using transgenic grain supplement at the level of 1 g/kg of feed with the standard recommended addition of the commercial enzyme preparation Avizyme 1100® at 1 g/kg yielded equal weight gain, feed consumption and feed efficiency in birds fed a barley-based diet. 6. The production of sticky droppings characteristic of broilers fed on barley diets was avoided with all 9 experimental diets and reduced to the level observed with a standard maize diet by supplementation with transgenic barley. 7. The excellent growth and normal survival of the 400 broilers tested on barley diets supplemented with transgenic grain or malt showed the grain and malt not to be toxic. 8. The barley feed with added transgenic grain or malt containing thermotolerant (1,3-1,4)-β-glucanase provides an environmentally friendly alternative to enzyme additives, as it uses photosynthetic energy for production of the enzyme in the grain and thus avoids use of non-renewable energy for fermentation. The deposition of the enzyme in the protein bodies of the grain in the field makes coating procedures for stabilisation of enzyme activity superfluous. 9. Barley feed with the small amount of transgenic grain as additive to normal barley provides an alternative for broiler feed in areas where grain maize cannot be grown for climatic reasons or because of unsuitable soil and thus has to be imported.