Feed Intake Of Mice Research Articles

Nitrogen‐Doped Multiwalled Carbon Nanotubes Trigger Immune Responses and Inhibit Fat Deposition

AbstractMultiwalled carbon nanotubes (MWCNTs) offer immense opportunities to deliver drugs and biomolecules to targeted tissues. However, it's unclear to their effects on fat metabolism. Here, it is demonstrated that nitrogen‐doped carboxylate‐functionalized MWCNTs (N‐MWCNTs) inhibit fat deposition both in vivo and in vitro. N‐MWCNTs <0.5 µg mL−1 do not affect the viability of HEK293 cells and adipose‐derived stem cells (ASCs). Intramuscular administration of N‐MWCNTs does not affect the body weight gain and feed intake of mice, but reduces the fat mass. In in vitro‐cultured adipocytes, N‐MWCNTs suppress fat accumulation, accompanied by decreased and increased expression of adipogenic and lipolysis genes, respectively. Transcriptome analysis further certifies the N‐MWCNT alteration of fat metabolism‐related genes. Interestingly, the internalization of N‐MWCNTs by macrophage‐like cells via Transmission electron microscopy (TEM) imaging is observed. The mRNA sequencing data also shows remarkable variation of the genes involved in the Toll‐like receptors (TLRs) pathway, exhibiting down‐ or up‐regulation of inflammatory factors, of which TNF‐α, IL‐1, IL‐7, IL‐10, and IL‐12 are decreased, whereas IL‐6 and IL‐11 are increased. In conclusion, N‐MWCNTs trigger immune responses and reduction of fat deposition.

Eugenol promotes appetite through TRP channels mediated-CaMKK2/AMPK signaling pathway.

Eugenol is a major component of clove oil. A recent study found that inhalation of eugenol promoted the appetite of mice. However, whether oral ingestion of eugenol promoted appetite is unclear and its mechanism await study. Here, mice were divided into four treatments (n=20) and fed a basal diet supplemented with 0%, 0.005%, 0.01% and 0.02% eugenol for 4 weeks. In addition, mice (n=7) were injected intraperitoneally with 3 mg/kg body weight eugenol. Our data showed that feeding mice with 0.01% and 0.02% eugenol promoted their appetite. In addition, the short-term intraperitoneal injection of eugenol enhanced the feed intake in mice within 1 h. Further studies found that dietary eugenol increased orexigenic factors expression and decreased anorexigenic factors expression in mice. We then carried out N38 cell experiments to explore the transient receptor potential (TRP) channels-dependent mechanism of eugenol in promoting appetite. We found that eugenol activated the TRP channels mediated-CaMKK2/AMPK signaling pathway in the hypothalamus and N38 cells. Besides, the inhibition of TRPV1 and AMPK eliminated the upregulation of eugenol on the agouti-related protein level in N38 cells. In conclusion, the study suggested that eugenol promotes appetite through TRPV1 mediated-CaMKK2/AMPK signaling pathway.

Selection for lower residual feed intake in mice is accompanied by increased body fatness and lower activity but not lower metabolic rate

Context Mice bred to be genetically different in feed efficiency were used in this experiment designed to help improve our knowledge of the biological basis of variation in feed efficiency between individual animals. Aims This experiment used mice to explore the metabolic basis of genetic variation in feed efficiency in the growing animal. Methods Mice bred to differ in residual feed intake (RFI) recorded over a postweaning test were used. After 11 generations of divergent selection, mice in groups were tested for RFI from 6 to 8, 8 to 10, and 10 to 12 weeks of age, and measured for traits describing the ability to digest feed, body composition, protein turnover, basal and resting metabolic rate, and level of activity. Key results Compared with the low-RFI (high efficiency) line mice, high-RFI mice consumed 28% more feed per day over their RFI-test, were no heavier, were leaner (16% less total fat per unit of bodyweight), did not differ in the fractional synthesis rate of protein in skeletal muscle or in liver, and had similar basal metabolic rates at 33°C. On an energy basis, the selection lines did not differ in energy retained in body tissue gain, which represented only 1.8% of metabolisable energy intake. The remaining 98.2% was lost as heat. Of the processes measured contributing to the higher feed intake by the high-RFI mice, 47% of the extra feed consumed was lost in faeces and urine, activity was 84% higher and accounted for 24%, the cost of protein gain was 6% higher and accounted for 2%, and the energy cost of digesting and absorbing the extra feed consumed and basal heat production could have accounted for 11 and 15% each. Conclusions Selection for low RFI (high efficiency) in mice was accompanied by an increase in body fat, an improvement in the process of digestion, a lower rate of protein turnover and a much lower level of activity. Selection did not result in major change in basal metabolic rate. Implications This experiment with mice provided new information on the biological basis of genetic differences in feed efficiency. The experiment investigated the relative importance of major energy-consuming metabolic processes and was able to quantify the responses in protein turnover and level of activity, being responses in energy-consuming processes that have proven difficult to quantitatively demonstrate in large farm animals.

Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m6A RNA Methylation.

Purpose: N 6-methyladenosine (m6A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m6A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m6A RNA methylation in the liver of mice. Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m6A modification in the liver were assessed. Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver. Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m6A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice.

An effect of dietary phloretin supplementation on feed intake in mice

Phloretin, abundantly present in apples, pears and other fruits, has been found to have antioxidant, immunosuppressive and anti-inflammatory activities. It has been reported that oral administration of phloretin dose-dependently increased feed intake in mice, but the mechanism is unclear yet. The aim of this study was to investigate the effect of dietary phloretin supplementation on the feed intake in C57BL/6J mice and to identify its mechanism. Here, sixty C57BL/6J mice (28-day age) were randomly chosen for four dietary treatments and fed a basal diet or a basal diet supplemented with 0.1%, 0.2%, and 0.3% phloretin, respectively, in a 6-week trial. We showed that mice in the 0.1%, 0.2%, and 0.3% phloretin-supplemented groups had increased accumulative feed intake compared with the control group. Furthermore, dietary phloretin supplementation significantly increased the ghrelin mRNA level in the stomach and hypothalamus, and decreased the cholecystokinin (CCK) mRNA level in the duodenum in a dose-dependent manner. The mRNA levels of neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin and melanocortin receptors 4 (MC4R), and pro-opiomelanocortin (POMC) in the hypothalamus were altered in response to dietary phloretin supplementation. Moreover, we confirmed that dietary phloretin supplementation reduced the expressions of miR-488 and miR-103, two feed intake-related miRNAs. Our present study provides evidence that dietary phloretin supplementation could increase feed intake in mice, which might be attributed to the stimulation of the hypothalamic feeding center via ghrelin, miRNAs (miR-103 and miR-488) and feeding signal factor-related genes (NPY, AgRP, MC4R and POMC), and to the inhibition of CCK to increase gastric emptying.

Nucleobindins and encoded peptides: From cell signaling to physiology.

Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two NUCBs, nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2), were discovered during the 1990s. These two peptides are shown to have diverse functions, including the regulation of inflammation and bone formation, among others. In 2006, Oh-I and colleagues discovered that three peptides encoded within the NUCB2 could be processed by prohormone convertases. These peptides were named nesfatin-1, 2 and 3, mainly due to the satiety and fat influencing properties of nesfatin-1. However, it was found that nesfatin-2 and -3 have no such effects. Nesfatin-1, especially its mid-segment, is very highly conserved across vertebrates. Although the receptor(s) that mediate nesfatin-1 effects are currently unknown, it is now considered an endogenous peptide with multiple functions, affecting central and peripheral tissues to regulate metabolism, reproduction, endocrine and other functions. We recently identified a nesfatin-1-like peptide (NLP) encoded within the NUCB1. Like nesfatin-1, NLP suppressed feed intake in mice and fish, and stimulated insulin secretion from pancreatic beta cells. There is considerable evidence available to indicate that nucleobindins and its encoded peptides are multifunctional regulators of cell biology and whole animal physiology. This review aims to briefly discuss the structure, distribution, functions and mechanism of action nucleobindins and encoded peptides.

Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and Impairs Barrier Function in Mice.

The purpose of this study was to explore relationships between low dose dietary supplementation with chitosan (COS) and body weight, feed intake, intestinal barrier function, and permeability in mice. Twenty mice were randomly assigned to receive an unadulterated control diet (control group) or a dietary supplementation with 30 mg/kg dose of chitosan (COS group) for two weeks. Whilst no significant differences were found between the conditions for body weight or food and water intake, mice in the COS group had an increased serum D-lactate content (P < 0.05) and a decreased jejunal diamine oxidase (DAO) activity (P < 0.05). Furthermore, mice in COS group displayed a reduced expression of occludin and ZO-1 (P < 0.05) and a reduced expression of occludin in the ileum (P < 0.05). The conclusion drawn from these findings showed that although 30 mg/kg COS-supplemented diet had no effect on body weight or feed intake in mice, this dosage may compromise intestinal barrier function and permeability. This research will contribute to the guidance on COS supplements.

Goji berry attenuates dextran sulfate sodium‐induced colitis

Inflammatory bowel diseases (IBD) including ulcerative colitis (UC) and Crohn's disease, are gastrointestinal disorders characterized by intestinal inflammation. Goji berry (Lycium barbarum), also known as wolfberry, is a traditional Chinese herbal medicine, which has long been recognized for its health beneficial effects such as antioxidative effects and diabetes prevention. Nonetheless, little is known regarding its effects in dextran sulfate sodium (DSS)‐induced colitis, a common colitis model of mice, which was investigated in this study. C57BL/6J male mice were first fed a standard rodent diet with or without 1% (w/w) goji berry for 4 weeks, then colitis was induced by supplementing 3% DSS in drinking water for 7 days, followed by a 7‐day recovery period to mimic symptoms of UC. Goji supplementation has no effects on body weight gain and feed intake in mice without DSS‐induced colitis. In DSS‐induced groups, Goji berry ameliorated body weight loss, diminished diarrhea and gross bleeding, resulting in a significantly decreased disease activity index associated with diminished DSS‐induced colon shortening. Histologically, Goji berry improved colonic edema, mucosal damage, and goblet cell depletion induced by DSS. In addition, Goji berry suppressed abnormal IL‐6 and COX2 mRNA expression, as well as apoptosis marker, active caspase‐3 content. In conclusion, for the first time, we demonstrate that dietary Goji berry supplementation confers protective effects against DSS‐induced colitis, suggesting a potential therapeutic value for IBD patients (NIH R15HD073864).

Direct response to selection for post-weaning net feed intake in mice and correlated responses in post-weaning growth, intake, gross digestibility and body composition

Seven generations of divergent selection on a phenotypic index of net feed in mice produced a realised heritability estimate of 0.27 ± 0.07. Despite small negative genetic correlations of net feed intake with daily gain and liveweight, correlated responses in these economically important traits were negligible. Still, more efficient animals tended to be fatter during the early post-weaning phase. Gross digestibility was also affected, which may have implications for the overall energy balance of a biological system.

The obesity gene in swine: sequence and expression of porcine leptin.

Leptin is a 16-kDa protein secreted by adipocytes that has been proposed to regulate feed intake in mice, rats, and humans. The present study was designed to characterize porcine leptin structure and expression. Successful RT-PCR resulted in development of a cDNA clone to the full length coding region of porcine leptin. Sequence data demonstrate 85% base homology to rodent, 88% to human, and a 92% homology to the bovine sequence. For assessment of porcine leptin gene expression, total RNA was extracted from the subcutaneous adipose tissue of genetically selected high backfat pigs and from contemporary crossbred swine. Total RNA derived from genetically selected high fat pigs contained 113% higher (P < .05) concentrations of porcine leptin mRNA than total RNA derived from contemporary crossbred pigs. Western blotting was used to evaluate serum levels of porcine leptin in genetically selected high backfat and contemporary, crossbred pigs. Relative levels of porcine leptin in sera from obese swine were approximately 306% higher (P < .05) than levels present in sera from contemporary, crossbred swine. These data indicate that leptin is expressed in pigs, the expressed protein is secreted into the bloodstream, and obese swine express higher levels of leptin mRNA and protein than nonobese swine at similar body weight.

In Vitro and Mouse Evaluation of Methods for Protecting Whey Protein and Casein from Ruminal Degradation

A series of in vitro buffer (protein solubility) and rumen fermentation (ammonia production) studies were conducted to evaluate varying formaldehyde (.25, .5, 1, and 3%) and tannic acid (.5, 1, 2, 3, and 6%), and three heating times (1, 2, and 3h at 104C) on protection of whey protein concentrate and casein from ruminal degradation. Subsequent trials of mouse growth were conducted to evaluate the effectiveness of protection of treated proteins. Formaldehyde (.25 to 3%) reduced solubility of whey protein and casein to less than 10% of the untreated in pH 6.8 buffer and approximately 30% of the untreated in pH 2.5 buffer plus pepsin. Formaldehyde reduced ammonia production, indicating protection and reduced solubility of whey protein and casein under rumen conditions in vitro. Tannic acid (.5 to 6%) did not greatly reduce protein solubility and ammonia production. Heat treatment reduced protein solubility to less than 10% of the untreated in pH 6.8 buffer and to 50% of the untreated in pH 2.5 buffer and reduced ammonia production to approximately 20% of the untreated. Growth and feed intake of mice were decreased with 1% formaldehyde treated diets (17% protein), indicating overprotection of protein. Growth decreased as tannic acid increased. Mouse growth also decreased as the length of heat treatment increased. Diets with .5% formaldehydecasein depressed gains. Based on these in vitro and mouse-evaluation studies, formaldehyde less than .5% of the dry weight is required to protect whey protein and casein from ruminal degradation and permit solubilization in the lower intestinal tract.