MAP3K5基因在畜禽剩余采食量表型调控中的研究进展

随着分子遗传学的发展,已经鉴定出了影响剩余采食量（RFI）的大量数量性状位点和候选基因。有丝分裂原活化蛋白3激酶5（MAP3K5）,也称凋亡信号调节激酶1（ASK1）,属于MAPK超家族基因之一。目前,已有细胞外信号调节蛋白激酶（ERK）、c-Jun N-末端激酶（JNK）和p38丝裂原激活蛋白激酶（p38-MAPK）这3个MAPK家族成员在哺乳动物细胞中被克隆和鉴定,其主要作用机制是介导3条MAPKs信号通路,从而影响家畜的生长、体型及产奶性状等。课题组在前期对RFI的研究中筛选出与牛剩余采食量相关的MAP3K5基因,但其功能作用尚不明确,笔者在此基础上回顾了该基因的结构、生物学功能,概述了该基因在主要畜禽采食量变异及人类肥胖表型中的功能及作用,并从遗传学的角度重点分析了MAP3K5基因在畜禽RFI表型调控中的可能机制。通过对MAP3K5基因在畜禽RFI表型调控中的研究进展进行综述,期望为后期深入开展MAP3K5基因在畜禽采食量性状调控中的分子机制研究提供思路;对于其他可能通过MAP3K5基因影响畜禽表型的因素（如肠道菌群）有待进一步探讨。     

Assessment of body fat in the pony: part I. Relationships between the anatomical distribution of adipose tissue, body composition and body condition

Reasons for performing study: Evaluation of equine body fat content is important for nutritional and clinical purposes. However, our understanding of total body fat and its regional distribution in the body is sparse. Currently, body fat evaluation relies on the subjective assessment of body condition score (BCS), which has never been validated against ‘gold standard’ chemical analysis or dissection measurements in ponies. Objectives: To define the relationships between subjective (BCS), objective (morphometric) indices of body fat and ‘gold standard’ measurements of actual body composition. Hypotheses: BCS and morphometry offer valid, noninvasive methods for determination of body fat in equids. Methods: Seven mature (mean ± s.e. 13 ± 3 years, 212 ± 14 kg, BCS 1.25–7/9), Welsh Mountain pony mares, destined for euthanasia (for nonresearch purposes), were used. For all ponies, body mass (BM), BCS and various morphometric measurements were recorded. Following euthanasia, all ponies were systematically dissected. Discrete white adipose tissue (WAT) depots were independently described. Gross, body chemical composition was determined by proximate analyses. Results: Total somatic soft tissues increased linearly (r²= 1.00), whereas body WAT content (1–26% live BM) increased exponentially (r²= 0.96), with BCS. WAT was equally distributed between internal and external sites in all animals irrespective of BCS. Nuchal fat was a poor predictor of total WAT (r²= 0.66). Periorbital WAT did not alter with BCS (r²= 0.01). Heart girth:withers height and ultrasonic retroperitoneal fat depth were closely associated with total, chemically‐extracted lipid which comprised 1–29% live BM (r²= 0.91 and 0.88, respectively). Conclusions and potential relevance: The exponential relationship between BCS and total body WAT/lipid suggests that BCS is unlikely to be a sensitive index of body fat for animals in moderate‐obese states. Morphometric measurements (body girths and retroperitonel fat depth) may be useful to augment subjective BCS systems.     

n‐3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose‐derived stem cells in vitro

Adipose‐derived stem cells (ADSCs) possess multipotent properties, and their proper functionality is essential for further development of metabolic disorders. In the current study, we explored the impact of two n‐3 LC‐PUFAs (long‐chain polyunsaturated fatty acids, DHA—docosahexaenoic; C22:6, and EPA—eicosapentaenoic; C20:5) on a specific profile of lipolytic‐related gene expressions in the in vitro‐differentiated subcutaneous and visceral ADSCs from rabbits. The subcutaneous and visceral ADSCs were obtained from 28‐day‐old New Zealand rabbits. The primary cells were cultured up to passage 4 and were induced for adipogenic differentiation. Thereafter, the differentiated cells were treated with 100 µg EPA or DHA for 48 hr. The total mRNA was isolated and target genes expression evaluated by real‐time RCR. The results demonstrated that treatment of rabbit ADSCs with n‐3 PUFAs significantly enhanced mRNA expression of Perilipin A, while the upregulation of leptin and Rab18 genes was seen mainly in ADSCs from visceral adipose tissue. Moreover, the EPA significantly enhanced PEDF (Pigment Derived Epithelium Factor) mRNA expression only in visceral cells. Collectively, the results suggest activation of an additional lipolysis pathway most evident in visceral cells. The data obtained in our study indicate that in vitro EPA up‐regulates the mRNA expression of the studied lipolysis‐associated genes stronger than DHA mainly in visceral rabbit ADSCs.     

Theoretical evaluation of risk for nutritional deficiency with caloric restriction in dogs

Background: Risk of nutrient deficiency in dogs during caloric restriction is not currently known, while obesity is a growing concern.

Objectives: To determine nutrients that might require further evaluation for the risk of deficiency during caloric restriction.

Animals and methods: Five commercially available canine diets, representing a range of caloric density (2900–4240?kcal/kg metabolizable energy), were assessed for potential nutrient inadequacy if fed to a hypothetical overweight dog. Caloric density and typical nutrient analysis for protein, amino acids, fat, fatty acids, minerals, and vitamins were obtained from the manufacturer. Nutrient intake was calculated using ideal body weight for caloric intakes including 87, 79, 70, 61 and 52?kcal/kg^0.75 and compared with National Research Council recommended nutrient allowances (NRC-RA) for ideal weight.

Results: No diets were less than NRC-RA when compared to NRC-RA (/1000?kcal). The five evaluated diets varied in terms of which nutrients were less than NRC-RA and the degree of restriction required for this to occur. All diets had at least one essential nutrient less than NRC-RA at 79?kcal/kg^0.75/day and multiple nutrients less than NRC-RA at 70?kcal/kg^0.75/day. Choline and selenium were the nutrients most often affected by caloric restriction but others were less than the NRC-RA with caloric restriction.

Conclusions: Further research is needed to determine actual nutrient requirements in overweight dogs, and whether clinical nutrient deficiencies actually arise in vivo.

Clinical importance: Weight loss plans for overweight dogs (particularly those with very low-energy requirements) should include consideration for nutrient adequacy.     

猪是研究肥胖及代谢综合征的理想模型

目前,肥胖在全球以惊人的速度增加,同时也是全人类面临的主要健康问题之一。研究者对于肥胖的研究进展是相当缓慢的,因为目前对肥胖的研究主要是以鼠作为动物医学模型,然而人与鼠之间在生理学上存在许多差异,比如脂肪酶、来普汀、抵抗素、肿瘤抑制因子α和其他细胞因子,从而很难将鼠的研究结果应用到人类身上。因此,研究者对发展另外一种动物医学研究模型非常地感兴趣,猪作为一种特殊的模型正快速地成为研究人类能量代谢和肥胖的生物医学模型,因为猪在出生后棕色脂肪会消失,具有与人类相似的代谢特征、心血管系统和适当的器官大小。本文综述了猪作为动物医学模型来研究肥胖和代谢综合征得到的结果,并与人进行了比较,特别强调了脂肪组织和细胞因子在调节能量平衡和肥胖相关炎症上的作用。     

QUALITATIVE ULTRASONOGRAPHY OF THE LIVER IN OBESE CATS

A prospective study was undertaken to compare the relative echogenicity of the liver and the fat of the falciform ligament in two groups of clinically normal obese cats. In the first group of cats, four of eight normal weight cats were fed a high calorie diet ad libitum for a 12 week period at which time they were considered obese. The liver was hyperechoic when compared to the adjacent fat of the falciform ligament in the obese cats. In the second group of cats, the body condition of a group of eight clinically normal cats was subjectively graded. On ultrasonographic examination, the liver of those cats considered to be overweight were hyperechoic compared to the adjacent fat of the falciform ligament. Results from this study suggest that clinically normal obese cats may have a liver that is hyperechoic relative to the fat of the falciform ligament.     

The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance

REASONS FOR PERFORMING STUDY: Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. HYPOTHESIS: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. METHODS: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sensitivity (IS) and pancreatic beta cell function while controlling for possible dietary and managemental influences on IR. RESULTS: Evidence of significantly improved IS and decreased pancreatic beta cell secretion was found following metformin treatment. The magnitude of effect was greater at earlier resampling (6-14 days) than at later times (23-220 days). Apparent subjective clinical benefits were good but less favourable than effects on IR. CONCLUSIONS: Metformin is safe and appears to increase IS in equids. POTENTIAL RELEVANCE: Metformin may be indicated as a treatment for IR in equids. Further studies are required to define appropriate selection of subjects warranting therapy, dosing schedule and pharmacokinetics.     

Myostatin null mice respond differently to dietary‐induced and genetic obesity

Our objective was to determine sensitivity of myostatin null (MN) mice to obesity induction by dietary or genetic means. To induce dietary obesity, 3‐week‐old wild type (WT) and MN mice were fed diets with 60% calories (HF) or 10% calories from fat (LF) for 4 weeks. MN mice did gain body fat on the HF diet but to a lesser extent than WT mice. Body weight and fat content was similar in MN mice fed HF and LF diets. To induce genetic obesity, the MN mutation was incorporated into leptin db/db (DB) mice generating mice homozygous for each mutation (MNDB). Nine‐week‐old MNDB mice were obese, similar to DB mice. Body weight, body fat content, fat pad weight and adipocyte size were all increased in MNDB mice compared to MN and WT mice and were quite similar to DB mice. However, fasting blood glucose, an indicator of insulin resistance and diabetes, was reduced in MNDB mice compared to DB mice. These results indicate that MN mice gain less body fat than WT on a HF diet, but the MN mutation does not alter fat accumulation caused by DB mutation. Thus, MN mice are not always resistant to obesity development.     

The effects of body weight,body condition score,sex, and age on serum fructosamine concentrations in clinically healthy cats

Background: Serum fructosamine (SF) concentrations depend on plasma glucose concentrations and are used to evaluate glycemic control in animals with diabetes mellitus (DM). Despite the strong association between obesity and DM, the effects of body weight (BW) and body condition on SF concentrations in clinically healthy cats have not been reported. Objective: The aim of the study was to evaluate the effects of BW, body condition score (BCS), sex, and age on SF concentrations in healthy cats. Methods: BW, BCS, and SF concentrations were determined in 84 clinically healthy client‐owned cats (50 neutered males, 33 spayed females, and 1 intact female) of known age. The cats were enrolled prospectively in the study. Results: Mean BW, median BCS, and mean SF concentrations for the 84 cats were 5.4 kg, 5/9, and 268.7±45.5 μmol/L (range 197–399), respectively. BW was weakly but significantly correlated with SF (r=.26; P=.02), whereas BCS was not. Cats weighing >5.4 kg and cats with BCS>5/9 had higher mean SF concentrations compared with cats weighing <5.4 kg and cats with BCS <5/9, respectively. Cats categorized as normal weight to obese by BW (BW≥4.0 kg) had higher mean SF concentrations compared with cats categorized as lean (BW<4.0 kg). For domestic shorthair cats, the same was true for BCS: cats with BCS≥4/9 had higher mean fructosamine concentrations than those with BCS<4/9. Male cats had significantly higher mean SF concentrations compared with female cats (285.1±45.3 vs 244.5±33.9 μmol/L, P<.001). Age did not affect mean SF concentrations. Conclusions: BW is positively correlated with SF concentration, and lean cats have lower SF concentrations than normal and obese cats. In contrast to previous reports, mean SF concentrations were higher in male cats than in female cats, even when males and females were matched based on BW, BCS, and age.     

A Comparative Study of Serum Biochemistry,Metabolome and Microbiome Parameters of Clinically Healthy,Normal Weight,Overweight, and Obese Companion Dogs

The aim of this study was to compare fecal microbiome, plasma, fecal and urine metabolomes, and serum biochemistry of adult companion dogs according to body condition scores. Blood, serum/plasma, urine, and fecal samples were collected from 66 clinically healthy, adult companion dogs of either normal weight (NW), overweight (OW), or obese dogs (OB). analyses included fecal microbiome analyses via 16S ribosomal RNA gene amplicon; sequencing, nontargeted plasma, fecal, and urine metabolomics using liquid chromatography/gas chromatography-mass; spectrometry, and serum biochemistry for each dog. Few significant differences in serum biochemistry and fecal microbiome Operational Taxonomic Unit (OTU) were found between weight groups and there was high OTU variation between individual dogs. NW dogs had higher relative abundance of the genus Eubacterium (log-fold change 4.3, adjusted P value?=?.003) and lower relative abundance of the family Bifidobacteriaceae (log-fold change ?3.6, adjusted P value?=?.02) compared to OB dogs. The microbiome of NW dogs had higher OTU richness compared with OB dogs. Metabolome analysis showed 185 plasma, 37 fecal, and 45 urine metabolites that significantly differed between NW and OW or OB dogs. There were notable significant differences in relative abundance of several plasma phospholipid moieties and fecal volatile fatty acids between weight phenotypes. The combinations of host and gut microbiota and metabolic shifts suggest a pattern that could help detection of early metabolic changes in overweight dogs before the development of obesity related disease. The results of this study support the need for continued investigation into sensitive measures of metabolic aberrancies in overweight dogs.