ACSL5 介导的脂肪酸代谢与癌症相关性研究进展

长链脂酰辅酶 A 合成酶系 (acyl-CoA synthetase long chain family, ACSLs) 催化辅酶 A (CoA) 与 12 ~ 20 个碳链长度的长链脂肪酸连接, 参与脂质的合成和代谢过程。 ACSL5 是唯一一种既位于线粒体上又 参与肠上皮细胞凋亡的 ACSLs 亚型, 在多种组织中都有表达。 已有许多关于不同癌症的研究报道 ACSL5 在 其中的表达明显不同于健康个体, 且 ACSL5 高表达对肺癌、 胰腺癌、 乳腺癌和卵巢癌患者的预后有积极影 响。 通过研究 ACSL5 参与的脂质代谢在癌症中的作用, 为靶向脂质代谢酶的癌症治疗提供新的靶点和策 略。     

羧胺三唑乳清酸盐对人胰腺癌细胞系增殖及脂肪酸合成代谢的影响

目的 研究羧胺三唑乳清酸盐(CTO)对人胰腺癌细胞增殖影响及对其脂肪酸合成代谢的调控作用。方法 以人胰腺癌细胞系AsPC-1、AsPC-1/GEM(简称AR)、PANC-1、MiaPaCa-2为研究对象,用磺酰罗丹明B(SRB)检测细胞存活率,采用qPCR检测胰腺癌细胞系中脂肪酸合成关键基因mRNA水平,用Western blot检测细胞内腺苷单磷酸依赖蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)通路蛋白表达;利用液相色谱-质谱联用代谢组学技术检测细胞内脂质代谢物质差异。结果 与对照组相比,CTO显著降低AsPC-1、AR、PANC-1、MiaPaCa-2 4株人胰腺癌细胞活率(P<0.05); CTO下调细胞内脂肪酸合成关键基因的mRNA水平(P<0.05);CTO下调细胞中AMPK、ACC及c-Myc蛋白表达(P<0.05),而增加p-AMPK、p-ACC蛋白表达(P<0.05);CTO减少AR细胞中脂质代谢物含量(P<0.05)。结论 CTO通过抑制癌基因c-Myc蛋白表达及AMPK/ACC通路,下调脂肪酸合成相关基因的表达活性,减弱细胞脂肪酸合...     

阿司匹林抑制冠心病患者外周血单核细胞脂肪酸合酶表达

<正>脂肪酸合酶(fatty acid synthase,FASN)是催化乙酰辅酶A和丙二酰辅酶A合成内源性长链脂肪酸的关键酶[1],单核巨噬细胞通过表面的CD36受体摄取氧化型低密度脂蛋白,在FASN的作用下形成泡沫细胞,干扰FASN基因可以显著减少泡沫细胞的生成。本研究探讨了阿司匹林对单核细胞脂肪酸合酶的影响。1材料与方法1.1材料1.1.1临床病例资料:收集2013年3月至2014年5月本院     

脂肪酸合成酶在肿瘤中表达的调节机制

脂肪酸合成酶(fatty acid synthase,FASN)是肿瘤脂质生成的一种关键酶,在催化脂肪酸合成的最后一步中发挥重要作用.FASN在许多肿瘤细胞中过表达而在相应的正常细胞中却不表达.有证据表明FASN是一个代谢性癌基因,在癌细胞中高表达,在肿瘤生长和存活中有重要的作用.FASN在肿瘤中的表达调节是一个很复杂的过程,包括转录水平、翻译后控制和微环境状态的影响.正确认识FASN在肿瘤中的表达调节机制和研究新的FASN抑制剂,为成功治疗肿瘤提供一种新的思路.     

短期高果糖喂养对小鼠肝脏脂质沉积和胰岛素敏感性的影响

目的: 探讨短期高果糖饮食对小鼠肝脏甘油三酯含量及胰岛素敏感性的影响。方法: 雄性C57BL/J6小鼠分为对照组及高果糖组,经喂养3 d后对小鼠行腹腔葡萄糖耐量试验,处死小鼠后测定各组肝脏甘油三酯含量,采用HE染色观察肝脏组织的病理改变;测定肝脏脂质合成酶类的蛋白表达,同时通过比较各组注射与未注射胰岛素的小鼠磷酸化Akt/总Akt (p-Akt/t- Akt)和磷酸化GSK-3α/β/总GSK-3α/β(p- GSK-3α/β/t- GSK-3α/β)表达变化评估肝脏胰岛素敏感性。结果: 喂养3 d后,与对照组相比,高果糖组葡萄糖耐量曲线下面积和肝腔甘油三酯均显著增加(均P<0.01),同时肝组织HE染色显示高果糖组小鼠肝细胞已有明显脂滴沉积;与对照组相比,高果糖组的乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(FAS)和硬脂酰辅酶A脱饱和酶-1(SCD-1)表达显著增加(均P<0.01);胰岛素注射后,与对照组相比,高果糖组的p-Akt/t-Akt及p-GSK-3α/β/t-GSK-3α/β均显著降低(均P<0.01)。结论: 3 d高果糖饮食即可引起肝脏脂质沉积,脂质沉积与果糖刺激FAS、ACC和SCD-1表达增加有关;肝脏脂质沉积的同时伴有肝脏胰岛素抵抗发生。     

乙酰辅酶A羧化酶1对胶质瘤细胞系U87细胞增殖、迁移和侵袭的影响

目的 探讨乙酰辅酶A羧化酶1（ACC1）对人胶质瘤细胞系U87细胞增殖、迁移及侵袭的作用。 方法 Western blotting检测人胶质瘤细胞系U87、U251及U373中ACC1的表达;构建ACC1过表达质粒载体,将过表达ACC1质粒载体瞬时转染至U87细胞中;Western blotting检测转染后U87细胞中ACC1表达情况;MTT实验检测过表达ACC1对U87细胞增殖的影响;Transwell迁移和侵袭实验分别检测过表达ACC1对U87细胞迁移和侵袭的影响;划痕实验检测过表达ACC1对U87细胞划痕愈合能力的影响;Western blotting检测相关蛋白表达变化。 结果 与人胶质瘤细胞系U251和U373相比,U87细胞中ACC1表达较低;ACC1过表达抑制U87细胞增殖（P<0.01）;ACC1过表达抑制U87细胞迁移、侵袭和划痕愈合能力（P<0.01）;ACC1过表达迁移和侵袭相关蛋白波形蛋白(vimentin)、纤维连接蛋白(fibronectin)和尿激酶型纤溶酶原激活剂(uPA)表达下调（P<0.01）,凋亡抑制蛋白Bcl-2和细胞周期蛋白(cyclin) B、cyclin D表达下调（P<0.01）,p-STAT3蛋白表达下调（P<0.01）,细胞周期蛋白P21表达上调（P<0.01）。 结论 过表达ACC1可能通过抑制STAT3活性,抑制人胶质瘤细胞的增殖、迁移和侵袭。     

脂肪酸合酶与脂肪酸代谢及细胞因子的关系

脂肪酸合酶(FASN),是一种大分子蛋白复合物,在内源性长链脂肪酸的合成中发挥着重要作用.研究证实脂肪酸代谢障碍可导致细胞因子的释放紊乱,与许多疾病发生相关,FASN的异常表达与某些疾病的发生、发展密切相关,尤其是在代谢性疾病如:肥胖、胰岛素抵抗中扮演了重要角色.本文对FASN蛋白的结构、功能、表达调控,以及与相关疾病细胞因子的关系进行了总结.     

CD147通过Akt/mTOR信号通路调控脂肪酸合成对子宫颈癌细胞增殖、侵袭和迁移的影响

目的 探讨CD147的表达对子宫颈癌细胞增殖、侵袭、迁移的影响和潜在的分子机制。方法 分析UCSC数据库BSG基因(编码CD147蛋白)在子宫颈癌中的表达,采用Log-rank test法评估各组表达的预后差异。应用Western blot法检测CD147在Siha、Hela和H8细胞中的表达,通过慢病毒转染Hela细胞下调CD147表达,并验证其转染效率。运用Western blot法检测各组细胞中p-Akt、p-mTOR、ACC1、FASN、E-cadherin和N-cadherin的表达;使用BODIPY染色和脂肪酸试剂盒检测细胞中脂肪酸含量;利用CCK-8、平板克隆和Transwell实验检测细胞增殖、侵袭和迁移能力。sh-CD147组经Akt激动剂(SC79)处理后,Western blot法检测细胞中p-Akt、p-mTOR、ACC1、FASN、E-cadherin和N-cadherin的表达;选用BODIPY染色和脂肪酸试剂盒检测细胞中脂肪酸含量;利用平板克隆实验和Transwell实验分别检测细胞增殖、侵袭和迁移能力。结果 UCSC数据库显示CD147在子宫颈癌中的表达...     

黄芪多糖通过活化AMPK和促进骨骼肌FAT/CD36转位改善成肌细胞FFAs代谢

 目的：探讨黄芪多糖(Astragalus polysaccharides, APS)对骨骼肌游离脂肪酸（free fatty acids, FFAs）代谢的影响及其机制。方法：培养小鼠C2C12成肌细胞;MTT法检测不同浓度FFAs作用不同时间对细胞活性的影响。根据MTT结果选取FFAs最适浓度和时间处理细胞并用APS干预,采用乙酰辅酶A合成酶-乙酰辅酶A氧化酶法检测APS干预前后培养液FFAs浓度;Western blotting测APS干预前后细胞膜脂肪酸转位酶(FAT/CD36)、总FAT/CD36、磷酸化腺苷酸活化蛋白激酶（phosphorylated AMP-activated protein kinase, p-AMPK）和总AMPK蛋白表达。结果：FFAs对细胞的毒性呈浓度和时间依赖性。与FFAs组比较,FFAs+APS组细胞膜FAT/CD36及p-AMPK蛋白表达增加(P<0.05),而总FAT/CD36及总AMPK蛋白表达无明显差异(P＞0.05),同时培养液FFAs浓度降低,细胞活性增加(P<0.05)。结论：APS可以增加骨骼肌细胞对FFAs的摄取利用,其机制可能与活化AMPK和促进FAT/CD36转位有关。     

二甲双胍降低高糖高胰岛素培养的MCF-7细胞中FASN的表达

脂肪酸合成酶(fatty acid synthase,FASN)是人体内脂肪酸从头合成途径的关键酶,在人体的能量代谢中起到了重要作用.研究发现,恶性肿瘤的FASN表达升高,并严重影响肿瘤的预后.二甲双胍用于治疗2型糖尿病的同时被证明有降低某些癌症风险的益处.本研究观察二甲双胍对高糖、高胰岛素环境中MCF-7细胞FASN表达的影响,探讨二甲双胍与肿瘤发生关系的可能机制.     

Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells

Background: Understanding the mechanisms of long chain fatty acid (LCFA) uptake in hepatic cells is of high medical importance to treat and to prevent fatty liver disease (FLD). ACSs (Acyl-CoA synthetases) are a family of enzymes that catalyze the esterification of fatty acids (FA) with CoA. Recent studies suggest that ACS enzymes drive the uptake of LCFA indirectly by their enzymatic activity and could promote special metabolic pathways dependent on their localization.The only protein located at the plasma membrane which has consistently been shown to enhance FA uptake is CD36.Aims: The current study investigated whether ACSs and CD36 could regulate hepatic LCFA uptake.Methods and Results: FATP2 and FATP4 were both localized to the ER of HuH7 and HepG2 cells as shown by double immunofluorescence in comparison to marker proteins. ACSL1 was located at mitochondria in both cell lines. Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. Quantitative FACS analysis showed a correlation between ACS expression levels and B12 uptake. FATP2 had the highest effect on B12 uptake of all proteins tested. CD36 was mainly localized at the plasma membrane. Whereas [3H]-oleic acid uptake was increased after overexpression, CD36 had no effect on B12 uptake.Conclusion: Uptake of LCFA into hepatoma cells can be regulated by the expression levels of intracellular enzymes. We propose that ACS enzymes drive FA uptake indirectly by esterification. Therefore these molecules are potential targets for treatment of nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH).     

Acetyl-CoA carboxylase and fatty acid synthase activities in human hypothalamus

Several data indicate that hypothalamic fatty acid synthesis pathway plays an important role in the control of food intake and energy expenditure in rodents. However, the confirmation of its physiological relevance in regulation of feeding in human remains incomplete. For fatty acid synthesis pathway to function as regulator of energy balance in human hypothalamus, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and other lipogenic enzymes activities must be present. The presence of FAS in human hypothalamic neurons has been shown by immunohistochemistry, but quantitative studies on FAS activity there has not been performed so far. There is no available data concerning ACC activity in human hypothalamus. Thus, we investigated ACC and FAS (as well as other lipogenic enzymes) activities in human hypothalamus of subjects who died in car accidents. The results presented in this paper indicate that ACC and FAS activities are present in human hypothalamus and that these activities are 2- to 3-fold lower than in rat hypothalamus. Moreover, our data presented in this paper indicate that other lipogenic enzymes activities are also present in human hypothalamus. The activity of FAS, ACC and other lipogenic enzymes in human hypothalamus suggests that fatty acid synthesis actively occurs there. Therefore, it is likely, that in human this pathway may be relevant to hypothalamic functioning as food intake and energy expenditure regulator, similarly as it was suggested in rodents.     

Metabolic alterations and targeted therapies in prostate cancer

Cancer cells synthesize de novo large amounts of fatty acids and cholesterol, irrespective of the circulating lipid levels and benefit from this increased lipid synthesis in terms of growth advantage, self-survival and drug resistance. Key lipogenic alterations that commonly occur in prostate cancer include over-expression of the enzyme fatty acid synthase (FASN) and deregulation of the 5-AMP-activated protein kinase (AMPK). FASN is a key metabolic enzyme that catalyses the synthesis of palmitate from the condensation of malonyl-CoA and acetyl-CoA de novo and plays a central role in energy homeostasis, by converting excess carbon intake into fatty acids for storage. AMPK functions as a central metabolic switch that governs glucose and lipid metabolism. Recent interest has focused on the potential of targeting metabolic pathways that may be altered during prostate tumorigenesis and progression. Several small molecule inhibitors of FASN have now been described or in development for therapeutic use; in addition, drugs that directly or indirectly induce AMPK activation have potential benefit in prostate cancer prevention and treatment.     

Subcellular distribution of key enzymes of lipid metabolism during the euthermia-hibernation-arousal cycle

Mammalian hibernation is a natural, fully reversible hypometabolic state characterized by a drastic reduction of body temperature and metabolic activity, which ensures survival to many species under adverse environmental conditions. During hibernation, many hibernators rely for energy supply almost exclusively on lipid reserves; the shift from carbohydrate to lipid metabolism implies profound rearrangement of the anabolic and catabolic pathways of energetic substrates. However, the structural counterpart of such adaptation is not known. In this study we investigated, by using immunoelectron microscopy, the fine intracellular distribution of two key enzymes involved in lipid metabolism, namely, the fatty acid synthase (FAS) and the long-chain fatty acyl-CoA synthetase (ACSL), in hepatocytes of euthermic, hibernating and arousing hazel dormice. Our results show that the two enzymes are differentially distributed in cellular compartments (cytoplasm, mitochondria and cell nuclei) of hepatocytes during euthermia. Quantitative redistribution of both enzymes among cellular compartments takes place during hibernation and arousal, in accordance with the physiological changes. Interestingly, this redistribution follows different seasonal patterns in cytoplasm, mitochondria and nuclei. In conclusion, our data represent the first quantitative morphological evidence of lipid enzyme distribution in a true hibernator throughout the year cycle, thus providing a structural framework to biochemical changes associated with the hypometabolism of hibernation.     

Acetate metabolism and aging: An emerging connection

Sirtuins are NAD⁺-dependent protein deacetylases that regulate gene silencing, energy metabolism and aging from bacteria to mammals. SIRT3, a mammalian mitochondrial sirtuin, deacetylates acetyl-CoA synthetase (AceCS2) in the mitochondria. AceCS2 is conserved from bacteria to humans, catalyzes the conversion of acetate to acetyl-CoA and enables peripheral tissues to utilize acetate during fasting conditions. Here, we review the regulation of acetate metabolism by sirtuins, the remarkable conservation of this metabolic regulatory pathway and its emerging role in the regulation of aging and longevity.     

Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased; however, the mechanisms involved in the pathogenesis of NAFLD have not been thoroughly investigated in humans. In this study, we evaluated the expression of fatty acid metabolism-related genes in NAFLD. Real-time RT-PCR was performed using liver biopsy samples from 12 NAFLD patients. The target genes studied were: acetyl-CoA carboxylase (ACC) 1, ACC2, and fatty acid synthase (FAS) for the evaluation of de novo fatty acid synthesis; carnitine palmitoyltransferase 1a (CPT1a), long-chain acyl-CoA dehydrogenase (LCAD), and long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase alpha (HADHalpha) for beta-oxidation in the mitochondria; peroxisome proliferator-activated receptor- (PPAR-) alpha and cytochrome P450 2E1 (CYP2E1) for oxidation in peroxisomes and microsomes (endoplasmic reticulum) respectively; and diacylglycerol O-acyltransferase 1 (DGAT1), PPAR-gamma, and hormone sensitive lipase (HSL) for triglyceride synthesis and catalysis. In NAFLD, expression of ACC1 and ACC2, but not FAS was increased, indicating that de novo fatty acid synthesis is enhanced in NAFLD. In contrast, expression of CTP1a, a rate-limiting enzyme, was remarkably decreased, indicating that beta-oxidation in the mitochondria was decreased, although the expression of LCAD and HADHalpha was increased. Expression of PPAR-alpha was increased, whereas that of CYP2E1 was reduced. The expression of DGAT1, PPAR-gamma, and HSL was enhanced. These data suggest that in NAFLD, increased de novo synthesis and decreased beta-oxidation in the mitochondria lead to accumulation of fatty acids in hepatocytes, although the extent of oxidation in peroxisomes and microsomes remains unclear.     

Novel Nuclear Localization of Fatty Acid Synthase Correlates with Prostate Cancer Aggressiveness

Fatty acid synthase is up-regulated in a variety of cancers, including prostate cancer. Up-regulation of fatty acid synthase not only increases production of fatty acids in tumors but also contributes to the transformed phenotype by conferring growth and survival advantages. In addition, increased fatty acid synthase expression in prostate cancer correlates with poor prognosis, although the mechanism(s) by which this occurs are not completely understood. Because fatty acid synthase is expressed at low levels in normal cells, it is currently a major target for anticancer drug design. Fatty acid synthase is normally found in the cytosol; however, we have discovered that it also localizes to the nucleus in a subset of prostate cancer cells. Analysis of the fatty acid synthase protein sequence indicated the presence of a nuclear localization signal, and subcellular fractionation of LNCaP prostate cancer cells, as well as immunofluorescent confocal microscopy of patient prostate tumor tissue and LNCaPs confirmed nuclear localization of this protein. Finally, immunohistochemical analysis of prostate cancer tissue indicated that nuclear localization of fatty acid synthase correlates with Gleason grade, implicating a potentially novel role in prostate cancer progression. Possible clinical implications include improving the accuracy of prostate biopsies in the diagnosis of low- versus intermediate-risk prostate cancer and the uncovering of novel metabolic pathways for the therapeutic targeting of androgen-independent prostate cancer.Fatty acid synthase (FASN) is a large, multifunctional enzyme that is responsible for the de novo synthesis of long chain fatty acids. Because it is typically unnecessary for FASN to produce fatty acids in cells because of sufficient intake of fatty acids in the diet, FASN is expressed at low levels in most normal tissues. However, FASN expression has been found to be up-regulated in many cancers¹, and in several cancers, including prostate cancer, it correlates with poor prognosis.^2–4 In immortalized human prostate epithelial cells and in the LNCaP human prostate cancer cell line, FASN expression increases cell proliferation and growth in soft agar and results in androgen receptor-dependent formation of invasive adenocarcinoma.⁵ That same study also reported that transgenic expression of FASN in mouse prostate epithelial cells led to prostatic intraepithelial neoplasia and protected against castration- and chemotherapeutic-induced apoptosis, whereas siRNA knockdown of FASN in LNCaP cells resulted in apoptosis.⁵A number of theories have been proposed to explain FASN up-regulation in cancers, which ultimately results in a metabolic shift toward producing large amounts of fatty acids. One such theory is related to the Warburg effect, a phenomenon that is observed in most cancers. This involves an increase in the use of the glycolytic pathway for energy production, which also leads to an increase in the substrates used in de novo fatty acid synthesis.^6,7 It has also been postulated that fatty acid production is necessary to supply the structural components of the cell membrane for actively proliferating tumor cells.⁷ Alternatively, in the hypoxic environment of tumors, FASN may provide a means for balancing redox through its ability to consume reducing molecules such as NADPH.^5–7 Regardless of the exact function(s) of FASN in carcinogenesis, it clearly contributes to the transformed phenotype by conferring growth and survival advantages.Although FASN is an attractive therapeutic target in the treatment of cancer because of its low level of expression in normal tissues and concomitant overexpression in many cancers, small molecule inhibitors designed against this oncogenic protein have experienced limitations in their effectiveness because of poor bioavailability, lack of specificity, and significant side effects.^7–10 To improve on therapeutics to target FASN, it is important to understand the precise mechanisms by which FASN promotes carcinogenesis.The normal location of FASN in the cytoplasm is consistent with its known role in fatty acid synthesis. However, when we were examining immunohistochemical images of FASN expression in prostate cancer specimens, we observed that FASN appeared to be localized to the nucleus in a subset of the tumor cells. Through examination of an online database (The Human Protein Atlas, http://www.proteinatlas.org, last accessed March 15, 2013) that contains patient prostate cancer sections subjected to multiple antibodies raised against FASN, nuclear localization of FASN in a subset of tumor cells was again observed. We sought to confirm the nuclear localization of FASN in prostate cancer and to determine whether it could be used as a clinical marker for this disease. To our knowledge, this is the first observation of FASN localizing to the nucleus in any cell type.     

Gastrointestinal stromal tumours overexpress fatty acid synthase

Fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is overexpressed in many malignant tumours and is associated with aggressive biological behaviour. FASN expression and its possible relationship with more aggressive behaviour in gastrointestinal stromal tumours (GISTs) have not been addressed to date. Here, FASN expression was assessed by immunohistochemistry in 60 primary GISTs (28 low/intermediate risk and 32 high risk) and seven metastatic GISTs. Sixteen smooth muscle gastrointestinal tumours were used as controls. FASN was overexpressed in 36 of 60 GISTs (60%): in 12 of 28 (42%) low/intermediate-risk GISTs and in 24 of 32 (75%) high-risk GISTs (p<0.05). Two primary and seven metastatic GISTs and five GIST cell lines (GIST882, GIST430, GIST522, GIST62, and GIST48), analysed by western blot, showed variable FASN expression. Most metastatic samples expressed high levels of FASN protein. Additionally, seven of 60 GISTs showed a proliferation rate higher than 10% by Ki67 and all of them expressed FASN (p<0.04). Finally, proliferation and apoptosis were investigated after FASN silencing in GIST882 cells, which displayed the highest FASN expression. siRNA-mediated FASN knock-down inhibited expression of the proliferation marker cyclin A, whereas no changes in p27 and cleaved PARP expression were seen. It is concluded that FASN is preferentially overexpressed in high-risk and metastatic GISTs, and that its overexpression likely contributes to cell proliferation.     

Fatty acid synthase gene regulation in primary hypothalamic neurons

Understanding the mechanisms that regulate feeding is critical to the development of therapeutic interventions for obesity. Many studies indicate that enzymes within fatty acid metabolic pathways may serve as targets for pharmacological tools to treat this epidemic. We, and others have previously demonstrated that C75, a fatty acid synthase (FAS) inhibitor, induced significant anorexia and weight loss by both central and peripheral mechanisms. Because the hypothalamus is important in the regulation of homeostatic processes for feeding control, we have identified pathways that alter the gene expression of FAS in primary hypothalamic neuronal cultures. Insulin, glucose and AICAR (an activator of AMP-activated protein kinase) affected changes in hypothalamic FAS mRNA, which may be regulated via the SREBP1c dependent or independent pathway.