The early life of nutrition is closely related to obesity and metabolic syndrome in adult.Lipid metabolic dysfunction is one of the important mechanisms in the development of adult diseases.Liver plays a key role in lipid metabolism.Hepatic lipid metabolism mainly includes fatty acid uptake,synthesis,esterification,oxidation and export.Exposed to a optimal nutrition environment in early life might lead to some adaptive effects in the liver and its organization structure,cell numbers and metabolic function.These adaptive responses might play a persistent effect in each way of hepatic lipid metabolism.Clarifying the programming effect of early nutrition on hepatic lipid metabolism and the relative molecular mechanism might provide related theoretical basis and practical molecular target for the prevention of adult diseases during childhood.

Objective To investigate the effect of neonatal overfeeding on the expression of lipid metabolic associated enzymes and molecular mechanisms in the livers of rats. Methods Male Sprague-Dawley rats were randomly assigned to litter sizes of three group ( small litters,SL group) or ten ( normal litters,NL group) on postnatal day 3. Body weight,milk intake,liver and fat pad (epididymal and retroperitonea) weight,and hepatic histological anal-ysis were recorded in week 2 and week 3,respectively. The levels of lipids were detected by the automatic biochemical analyzer. The mRNA expressions of acetyl-CoA carboxylase ( ACC) ,lipoprotein lipase ( LPL) ,liver-type fatty acid-binding protein (L-FABP), carnitine palmitoyltransferase 1(CPT1),microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator activated receptorα(PPARα) in liver were determined by real time PCR;the protein expressions of SREBP-1c and PPARα were determined by Western lot. Results As early as week 2,the body weight of rats in SL group began to elevate (t=-5. 997,P<0. 001) and food intake (t=-3. 462,P=0. 002) compared with the rats in NL group,and persistent to weaning (body weight:t=-17. 019,P<0. 001;food intake:t=-2. 276,P=0. 031). By the time of 3 weeks old,SL rats increased visceral fat pad [ret-roperitonea (t=-7. 643,P<0. 001),epididymal (t=5. 997,P=0. 001)],liver weight (t=-7. 812,P<0. 001),hepatosomatic index (t=-3.829,P=0. 003) and serum triglyceride (TG) level (t=-2. 703,P=0. 022) compared with those of NL rats,as well as the level of hepatic ACC mRNA (t=-3. 751,P=0. 007),LPL (t=-2. 721,P=0. 017) and L-FABP mRNA (t=-2. 521,P=0. 026) . While CPT1 mRNA (t=-1. 531,P=0. 155) and MTP mRNA (t=-1. 741,P=0. 098) levels remained unchanged in both groups. Hepatic SREBP-1c mRNA expression increased in SL rats after 2 to 3 weeks (t=-2. 836,P=0. 016),paralleled with ACC and LPL mRNA expression;while the mRNA and protein expression of PPARα re-mained unchanged (t=-0. 854,P=0. 411). Conclusions Postnatal overfeeding can promote higher liver pad and dyslip-idemia at the time of weaning. The process may be regulated by up-regulated expression of ACC, LPL and L-FABP. SREBP-1c may be participated in the regulation of ACC,a rate-limiting enzyme involved in lipogenesis.

Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats,and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding.Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table.After weaning at postnatal week 3,the rats were randomly given standard chow or high-fat (HF) diet until week 16.Hence four groups were analyzed,namely normal feeding group,breastfed overfeeding group,post-weaning overfeeding group,and continuous overfeeding group.Body weight was continuously monitored in each week.Visceral fat pad (retroperitoneal and perigenital),systolic pressure,and heart rate were observed at week 3 and week 16.Thoracic aorta was sampled for measurement of vascular endothelial dilation function.Histological morphology was observed with HE staining,nitric oxide content of thoracic aorta was detected with nitrate reductase method.The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction.The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot.Results At week 3,breastfed overfeeding rats displayed significantly larger body weight [(77.80 ± 0.57) g vs.(62.80 ±0.85) g,t =14.576,P ＜ 0.01] and visceral fat [retroperitoneal:(8.19 ± 0.49) mg/g vs.(4.92 ± 0.31) mg/g,t =5.629,P＜0.01;perigenital:(3.50 ±0.29) mg/g vs.(2.08 ±0.13) mg/g,t =4.552,P ＜0.01] compared with normal feedindg rats,and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F =15.215,P ＜0.01);high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats.At week 16,continuous overfeeding rats showed hypertension [(149 ± 1.94) mmHg (1 mmHg =0.133 kPa),F =22.834,P ＜0.01],impaired vascular endothelial dilation function (F =7.648,P ＜ 0.05),and reduced protein expression of phosphorylated eNOS (F =15.215,P ＜ 0.01),while the post-weaning overfeeding group only had elevated blood pressure.Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension.The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding.

Objective To observe ghrelin expression in gastric tissue and serum leptin level of the early over-fed rats given ω-3 polyunsaturated fatty acids (PUFAs) diets after weaning,and explore the effects of early over-feeding and diets intervention on the metabolic syndrome in adult rats.Methods Male Sprague-Dawley rats were divided into normal feeding group (NF group,10 per litter) or over-feeding group (OF group,3 per litter) in postnatal day 3,and then different diets were given after weaning (postnatal day 21).The OF group was separately given conventional diet (OF + Con group),high-fat diet (OF + HF group),or ω-3 PUFAs (OF + ω-3 group) ; while the NF group was separated into NF + Con group and NF + HF group.Body weight and food intake were recorded every week.In week 6 and week 16,glucose tolerance test was perforfmed.Serum leptin,ghrelin,and triglyceride were assayed by enzyme-linked immuno-absorbent assay.Ghrelin mRNA and protein levels in gastric tissue were quantified by real-time PCR and immunohistochemistry.Results At week 16,energy intake,body weight and glucose intolerance in OF + HF group were significantly higher than in NF + HF group (t =-3.453,P =0.014 ; t =-6.406,P =0.000 ; F =16.249,P =0.000),and serum triglycerides,ghrelin mRNA of gastric tissue were significantly higher than those of OF + Con group (t =4.72,P =0.005 ; t =8.486,P =0.000).At week 16,the serum leptin level in OF + Con group was higher than that in NF + Con group (t =-3.274,P =0.031),also higher in OF + HF group than that in OF + Con group (t =3.028,P =0.014).There were no significant differences in serum ghrelin and the area of ghrelin immuno-positive cells in the gastric tissue among groups.The above indicators in OF + ω-3 group were not different from those of NF + Con group.Conclusions Over-feeding during the lactation period may lead to high susceptibility to obesity and disordered glucose and lipid metabolism.It can also increase serum leptin and ghrelin mRNA expression in gastric tissue,aggravate leptin resistance and feeding control disorders.Dietary ω-3 PUFAs offered protection against excessive accumulation of adipose tissue,glucose intolerance,leptin resistance,and maintained normal levels of leptin and ghrelin.

Objective To assess the local treatment efficacy of percutaneous radiofrequency ablation(PRFA) in combination with percutaneous ethanol injection(PEI) therapy protocol for liver metastases in patients with colorectal cancer.Methods From February 2000 to February 2004, total of 61 liver metastatic lesions(1.5～7.8 cm) from 37 colorectal cancer patients were ablated by using RF-2000 generator and 10-needle LeVeen electrode percutaneously guided by B-ultrasound.Tumors larger than 2.5 cm in diameter were treated by multiple overlapping radiofrequency ablations encompassing the entire lesion as well as a rim of normal liver tissue(approximately 1.0 cm).PEI was performed additionally.The Chiba needle and Quadra-Fuse multi-pronged injection needle were used for tumors ranged 1～2 cm and for those larger than 3 cm respectively.Results The procedures were performed successfully in all patients.The post-PRFA/PEI complication rate was 5.4%.The follow-up rate was 97.3%(36/37).Thirteen patients achieved a complete response(CR),and 21 achieved a partial response(PR).The effective rate(CR+PR) was 94.4%.The patients' survival rates were 97.2% at 1 year,75.0% at 2 years,and 52.8% at 3 years respectively.Conclusion The results of this study suggest that the treatment protocol of PRFA in combination with PEI was an effective mini-invasive local ablation therapy,which was part of the comprehensive management of the colorectal liver metastases.