Prevention and Treatment of NAFLD with Traditional Chinese Medicine Monomers by Regulating AMPK Pathway： A Review / 中国实验方剂学杂志

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

The molecular mechanism of ginkgolide B regulating the expression of long-chain fatty acid metabolism-related proteins and antioxidant therapy for non-alcoholic fatty liver disease / 药学学报

This study investigated the effects of ginkgolide B on the long-chain fatty acid metabolism-related enzyme protein peroxisome proliferators-activated receptors α (PPARα), long-chain specific acyl-CoA dehydrogenase (LCAD), carnitine palmitoyl transterase-1 (CPT-1), and acyl coenzyme A oxidase 1 (ACOX1) expression in the liver of rats with non-alcoholic fatty liver disease (NAFLD). All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of Yunnan University of Traditional Chinese Medicine. After successfully building the rat model of non-alcoholic abnormal liver disease, the rats were divided into the model group, the simvastatin group, and the low-dose, middle-dose, and high-dose groups of ginkgolide B according to random number method, and were given corresponding drug treatment 4 weeks. We detected liver pathological indicators and determined blood lipids, transaminase and anti-oxidation indexes. Western blot and RT-PCR assays were used to detect the protein and mRNA levels of PPARα, LCAD, CPT-1, and ACOX1 in livers. The results showed that: ① the liver histopathology showed that the liver slices of the model group had obvious structural disorder, the nucleus was squeezed, and there were obvious fat vacuoles. The treatment groups improved significantly compared with the model group; ② compared with the normal group, the liver function and blood lipid indexes of the model group increased significantly, while the anti-oxidation indexes decreased significantly. Compared with the model group, each treatment groups were significantly improved; ③ compared with the normal group, the protein and mRNA expression levels of PPARα, ACOX1, CPT-1, and LCAD in the model group were significantly reduced, compared with the model group, those indexes in the treatment groups were significantly up-regulated. This study found that ginkgolide B could regulate the expression of long-chain fatty acid metabolism-related proteins PPARα, ACOX1, CPT-1, and LCAD, meanwhile improve the body's antioxidant capacity, thereby reduce blood lipids, further improve liver function and protect the liver.

Research Progress of Celastrol in Obesity / 中国药学杂志

Obesity is a kind of metabolic disease, which is a major risk factor of heart disease, diabetes mellitus and cancer. In recent years, the US Food and Drug Administration (FDA) has approved a stand of drugs treatment for obesity, including sibutramine, orlistat, belviq and so on,however, side effects may occur after long-term using. Celastrol is a class of pentacyclic triterpenoids extracted from the roots of Tripterygium wilfordii Hook F. It has been found that celastrol has the pharmacological activities of increasing leptin sensitivity, increasing fat metabolism, inhibiting the formation of lipocyte and inhibiting chronic inflammation in obesity animals. This overview summarizes the related mechanisms of celastrol on treatment of obesity to provide enlightenments for its further study.

Srebps: a potential therapeutic target for metabolic diseases / 中国药学杂志

Sterol regulatory element binding proteins (SREBPs) are the major transcription factors regulating cholesterol, fatty acid and triglyceride biosynthesis and control the expression of key genes such as lipogenesis and uptake. In this review, we summarize the processing of SREBPs and their interactions with insulin, cyclic adenosine monophosphate (cAMP), and liver X receptor (LXR) for the synthesis and metabolism of lipid, and combine the latest researches to illustrate the function of SREBPs. These findings suggest that inhibition of SREBPs can be a new strategy for the treatment of metabolic diseases, such as type Ⅱ diabetes, insulin resistance, fatty liver, atherosclerosis and tumors.

On the regulation of bone metabolism: A research review of neuropeptide Y / 中华内分泌代谢杂志

Skeleton metabolic diseases such as osteoporosis and fracture have posed an detrimental impact on the elderly, which is a primary cause of paralysis and even death in patients. Osteoblast and osteoclast are the two major parts in the regulation of bone homeostasis and imbalance of these two cells, which may result in dysfunction of bone metabolism. Recent researches indicated that bone homeostasis was primarily regulated by endocrine, paracrine, and local mechanical processes. However, increasing evidences have indicated that the significant role of nerve system may involve in bone metabolism via both central and peripheral pathways. Neuropeptide Y(NPY), a neurotransmitter that belongs to a family of peptides,serves as a critical hinge connecting nerve system and skeleton system. Several studies have suggested that NPY generated by both central and peripheral nerve system could regulate bone homeostasis and that NPY-energic nerve fibers distributed on bone surface and in intramedullary cavity and NPY receptors located at osteoblast, chondrocyte, and osteocytes also provide a basis for nerve-skeleton metabolic pathways. NPY can directly regulate osteoprogenitor, involving in the production and differentiation of osteoblast and osteoclast. In addition, as a pivotal molecular of energy homeostasis, NPY may affect glucose and fat homeostasis. Studies of animal models also have further indicated energy metabolism may directly or indirectly participate in the regulation of bone mass. Therefore, further researches on the relationship between NPY and bone homeostasis may facilitate to unveil the central and peripheral regulatory effect of NPY on bone homeostasis and provide a new sight for the treatment of skeleton metabolism-related diseases in the future.

Effect of Fuzi Lizhong decoction in reducing liver injury of rats with non-alcoholic fatty liver via activating AMPK and suppressing NF-κBp65 pathway / 中国中药杂志

To investigate the protective effect and relevant mechanism of Fuzi Lizhong decoction (FZLZD) on liver of rats with non-alcoholic fatty liver disease (NAFLD), totally 32 male SPF Wistar rats were randomly divided into 4 groups: control group, model group, Yishanfu (YSF) group (200 mg·kg⁻¹·d⁻¹) and FZLZD group (10 g·kg⁻¹·d⁻¹), with 8 rats in each group. Rat model of NAFLD was prepared through the intragastric administration with fat emulsion for 4 weeks. After the successful modeling, rats in each administration group were continuously administered for 4 weeks. After 8 weeks, the rats in each group were put to death, and the pathological changes in liver tissue were detected by HE staining. Automatic biochemical analyzer was used to detect fasting serum lipid levels (T-Chol, TG, LDL-C, HDL-C) and liver functions (ALT, TP, ALB) of rats in each group. The rat liver index was calculated by weighing method. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of inflammatory cytokines TNF-α and IL-6 in liver tissue. Real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expressions of fat metabolism-related factors SREBP-1c and FASN in liver tissue. Western blot was used to detect the p-AMPK and p-NF-κBp65 protein expressions in liver tissue. The results of HE staining showed that compared with the control group, the pathological changes in liver tissue in the model group rats were obvious; specifically, the outline of hepatic lobule was unclear, the hepatic cells showed diffuse steatosis of adipose tissue, and were accompanied by inflammatory infiltration, nuclear condensation, coloring deep; compared with the model group, liver lesions of all of the treatment groups were significantly alleviated; especially, the FZLZD group showed the most significant degree of remission. The results of serum test showed that the levels of serum lipids (T-Chol, TG, LDL-C, HDL-C), liver functions (ALT, TP, ALB) and liver index in model group were significantly higher than those in control group (<0.01); compared with the model group, the indexes of serum lipid and liver function of rats in each treatment group were significantly decreased (<0.01), and those in FZLZD group were significantly decreased (<0.05), while those in YSF group were not significantly changed. The results of ELISA and qRT-PCR showed that compared with the control group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c and FASN in the liver tissue of model group rats were significantly increased (<0.01); compared with model group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c, FASN in liver tissue of rats in each treatment group were significantly decreased (<0.01); compared with YSF group, the secretion levels of TNF-α and IL-6 and the mRNA levels of SREBP-1c and FASN in FZLZD group were significantly different (<0.01). Western blotting showed that compared with the model group, the protein expression of p-AMPK in liver tissue of rats in FZLZD group was significantly increased (<0.01), while the protein expression of p-NF-κBp65 was significantly decreased (<0.01). FZLZD can significantly improve hepatic pathological changes, reduce serum lipid levels, promote liver function and liver index in NAFLD rats, which may be associated with the activation of the AMPK pathway and thereby the inhibition of the expressions of SREBP-1c and FASN, and the inhibition of the NF-κBp65 pathway and thereby the reduction of the release of inflammatory factors.

Effects of ω-3 polyunsaturated fatty acids on fat metabolism and bone metabolism / 中华内分泌代谢杂志

There are mounting evidences demonstrating that obesity and osteoporosis pose a daunting threat on global public health problem, given their morbidity and mortality. Ω-3 polyunsaturated fatty acids ,besides as a source of energy, may regulate the cellular signal transduction pathway to produce specific patterns of gene expression, and protect from complications of obesity and osteoporosis . This article reviewed the correlation between obesity and osteoporosis, and summarized the effects and potential mechanism of ω-3 polyunsaturated fatty acids on fat metabolism and bone metabolism from both animal experiments and epidemiological studies.

Relato de caso: doença de Madelung / Case report: Madelung's disease

A síndrome de Madelung ou também conhecida por lipomatose simétrica múltipla (LSM) é uma lipodistrofia benigna rara que se caracteriza por múltiplas massas adiposas não encapsuladas. Ainda de etiologia desconhecida, existe a suspeita de uma possível herança autossômica dominante. Está fortemente associada ao abuso de álcool (60-90% dos casos). Apresenta curso clínico variável, de crescimento rápido com posterior estabilização ou progressão lenta. Pode ser assintomática ou causar sintomas de compressão de estruturas mediastinais e do trato aerodigestivo. O tratamento de escolha é cirúrgico (AU)

Madelung syndrome, also known as multiple symmetric lipomatosis (MSL), is a rare benign lipodystrophy that is characterized by multiple non-encapsulated adipose masses. Although of unknown etiology, there is a suspected autosomal dominant inheritance. It is strongly associated with alcohol abuse (60-90% of cases). It presents a variable clinical course, of fast growth with later stabilization or slow progression. It may be asymptomatic or cause symptoms of compression of mediastinal structures and aerodigestive tract. The treatment of choice is surgical (AU)

C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans

Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

Role of carnitine transporter in skeletal muscle energy metabolism / 体力科学

In skeletal muscle, carnitine is essential for the translocation of long-chain fatty-acids into the mitochondrial matrix for subsequent β-oxidation, and in the regulation of the mitochondrial acetyl coenzyme A/ free coenzyme A ratio by buffering excess acetyl groups. Based on the concept that increased carnitine availability is beneficial to skeletal muscle metabolic process, a large amount of research was directed towards investigating the effects of carnitine supplementation on exercise performance. However, it has been debated about contribution of carnitine for energy metabolism in skeletal muscle and whether carnitine supplementation can improve physical performance in healthy subjects. Recently, in order to resolve the issues, attention has been focused on the carnitine transport mechanism across the skeletal muscle plasma membrane. Due to lack of endogenous synthesis of carnitine in myocytes, skeletal muscles need to import this molecule from blood, suggesting that muscle carnitine uptake is most likely the limiting factor to muscle carnitine availability. It has been established that the specific carnitine transporter, OCTN2, is expressed in skeletal muscles and is assumed to transport carnitine into myocytes. Carnitine uptake capacity via the OCTN2, therefore, has been assumed to be one of the important factors to the skeletal muscle energy metabolism. The purpose of the review is to summarize the role of carnitine in skeletal muscle metabolism, and the current knowledge regarding the effect of carnitine supplementation of exercise performance. Furthermore, we summarize recent observations related to the carnitine transport mechanism in skeletal muscles including contribution of OCTN2 during muscle contraction.

Effect of erva-mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) on serum cholesterol, triacylglycerides and glucose in Wistar rats fed a diet supplemented with fat and sugar / Efeito da erva-mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) sobre o colesterol, triacilglicerídeos e glucose em ratos Wistar com dieta alimentar suplementada com lipídeos e glicídeos

Ilex paraguariensis A. St.-Hil., Aquifoliaceae, is a species native to the subtropical and temperate regions of South America, used in beverages prepared by infusion such as teas, chimarrão and tererê. To investigate the physiological effects of I. paraguariensis on the metabolism of fats and sugars in Wistar rats, following the ingestion of erva-mate tea, four experimental groups were constructed: Lipid Control Group (receiving water and high-fat diet); Lipid Tea Group (extract of I. paraguariensis and high-fat diet); the Sugar Control Group (water and high-sugar diet); and Sugar Tea Group (extract of I. paraguariensis and high-sugar diet). The animals received their particular diet for 60 days, and were weighed weekly. After this period, the plasma concentrations of cholesterol, glucose and triacylglycerides were determined, together with the weight of visceral fat. The data were subjected to statistical analysis with a significance level of p<0.05. The results show that the ingestion of erva-mate affected body weight, visceral fat and plasma glucose, cholesterol and triacylglyceride levels.

Ilex paraguariensis A. St.-Hil., Aquifoliaceae, é uma espécie nativa das regiões subtropicais e temperadas da América do Sul, usada em bebidas por infusão como chá, chimarrão e tererê. Para verificar os efeitos fisiológicos que a I. paraguariensis pode causar sobre o metabolismo de lipídeos e glicídeos em ratos Wistar, após a ingestão de chá de erva-mate, analisou-se quatro grupos experimentais: Grupo Lipídeo Controle (receberam água e dieta hiperlipídica); Grupo Lipídeo Ingestão (extrato de I. paraguariensis e dieta hiperlipídica); Grupo Glicídeo Controle (receberam água e dieta hiperglicídica); e Grupo Glicídeo Ingestão (extrato de I. paraguariensis e dieta hiperglicídica). Os animais receberam a dieta por 60 dias, de acordo com o grupo que pertenciam, sendo pesados semanalmente. Após esse período, foram avaliadas as concentrações de colesterol, glicose e triacilglicerídeos sanguíneos, e ainda, peso da gordura visceral. Os dados foram analisados estatísticamente. O nível de significância aceito foi p<0,05. Os resultados mostraram que a ingestão de erva-mate atua sobre o peso corpóreo, gordura visceral e taxas de glucose, colesterol e triacilglicerídeos plasmáticos.

Establishment of cell line stably expressing INSIG2 and its effects on fat metabolism / 基础医学与临床

Objective To establish the cell line stably expressing INSIG2 and observe its effecet on fat metabolism after overexpression of INSIG2.Methods The eukaryotic expression plasmid pcDNA3.1(+)-INSIG2 was constructed,which was transfected into 3T3-L1 cells.The expression of INSIG2 and related genes were detected by RT-PCR and immunohistochemistry,the contents of FFA in cell culture medium and adipocyte differentiation were detected by ELISA and Oil Red "O"staining respectively.Results After pcDNA3.1(+)-INSIG2 was transfected into the 3T3-L1 cells,the expression of INSIG1 mRNA and FAS mRNA were down-regulated,the content of FFA in the cell culture medium was decreased and adipocyte differentiation was drepressed.Conclusion The cell line stably expressing INSIG2 was successfully established,the transfected INSIG2 may have a drepressant effect on fat metabolism.

Experimental study on correlation of ICAM-1 and fat metabolism with steroid femur head necrosis / 解放军医学杂志

Objective To study the intercellular adhesion molecule-1(ICAM-1)and fat metabolism in the contribution of the incidence of steroid avascular necrosis of femoral head(ANFH).Methods 32 New Zealand rabbits were randomly divided into two groups:animals in experiment group(n=24)were given an injection of hydrocortisone acetate(8.0mg/kg)two times per week,and animals in control group(n=8)were given an injection with the same volume of normal saline.Serum total cholesterol(TC),triglyceride(TG)and ICAM-1 were quantitated before and 2,4,6,8 weeks after the treatment.2,4,6 and 8 weeks after treatment,6 animals of the experiment group and 2 of the control group were randomly chosen and sacrificed.ICAM-1 expression in soft tissue around hip was determined immunohistochemically,and pathohistological changes in femoral head were observed by light microscopy.Results Serum TC and TG levels of the animals in experimental group were significantly higher than those before treatment and those in control group in the 6th week after treatment(P

Changes in serum glucocorticoid and lipid metabolism in rabbits with steroid avascular necrosis of femoral head / 解放军医学杂志

Objective To explore the effects of glucocorticoid(GC)and lipid metabolism on the pathogenesis of avascular necrosis of femoral head(ANFH).Methods Thirty-two New Zealand rabbits were randomly assigned into two groups as experiment group(n=24)and control group(n=8).Each rabbit in experiment group was given injection with 8.0mg/kg of hydrocortisone acetate for two times per week,while rabbits in control group were given normal saline in same quantity.Serum glucocorticoid(GC)concentration,total cholesterol(TC)and triglyceride(TG)were determined respectively before and 2,4,6 and 8 weeks after treatment.Rabbits were sacrificed at the 2nd,4th,6th and 8th week.The rabbits,sacrificed at the same time point,were stratified into group A(low concentration group)and group B(high concentration group)according to the GC concentration,in an attempt to observe the rate of empty bone lacuna and glucocorticoid receptor(GR)expression in the soft tissue around hips.Results The concentration of TC of experiment group began to increase since the 6th week,and that of TG since 2nd week(P0.05).In addition,the rate of bone lacuna and OD scores of GR were positively correlated at the 4th and 8th week(r=0.699 0,0.605 0,P