The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States

Fuhui Li; Wenqing Shen

doi:doi:10.11648/j.sr.20261406.12

Research Article |

| Peer-Reviewed

The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States

Fuhui Li

, Wenqing Shen^*

Published in Science Research (Volume 14, Issue 6)

Received: 10 August 2026 Accepted: 4 October 2026 Published: 10 November 2026

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Abstract

Obesity and type 2 diabetes mellitus, as major epidemiological research topics, have become global public health concerns that profoundly impact human health. According to data from the 2025 report of the National Health Commission of China, based on body mass index (BMI) and body fat percentage measurements, the prevalence of overweight among Chinese adults reached 34.3%, while the prevalence of obesity was 16.4%, yielding a combined overweight and obesity rate of 50.7%. Chronic positive energy balance, resulting from energy intake exceeding energy expenditure, leads to disruption of energy homeostasis, thereby promoting the development of chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Among these, obesity and type 2 diabetes induce disorders of glucolipid metabolism and mitochondrial dysfunction, with lipid metabolic disturbances being the most prominent. This review primarily focuses on the effects of various exercise modalities combined with pharmacological interventions on adipokine profiles in obese patients or rodent models, as well as the roles of the TGF-β/Smad2/3 and AMPK/UCP1 signaling pathways in lipid metabolism. We conclude that the combination of exercise and drug therapy effectively suppresses adipokine secretion and inhibits TGF-β/Smad2/3 signaling, thereby attenuating lipogenesis, while concurrently activating the AMPK/UCP1 pathway to enhance lipolysis. Therefore, exercise combined with pharmacological treatment can effectively regulate adipokine secretion and modulate the TGF-β/Smad2/3 and AMPK/UCP1 signaling cascades, offering a promising strategy for the prevention and treatment of obesity and other metabolic disorders.

Published in	Science Research (Volume 14, Issue 6)
DOI	10.11648/j.sr.20261406.12
Page(s)	395-405
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2026. Published by Science Publishing Group

Keywords

Obesity, Exercise, Lipolysis, TGF-β/Smad2/3, AMPK/UCP1

1．引言

随着国家经济、政治、文化和绿色生态的快速发展，人民物质文化生活的极大丰富，摆脱经济落后、食物短缺的历史局限，食物种类和质量的大幅提高，也伴随高糖高脂油炸食物的大量兴起，增加的工作压力和繁忙的生活导致人们体力活动水平下降，体育锻炼或运动时间大幅缩短，进而导致肥胖、2型糖尿病、高血压、非酒精性脂肪肝等代谢类疾病的高发[1, 2]。截止于2025年世界肥胖日报告指出全球68%人口至少处于超重状态，成人肥胖率达12.5%，预计到2030年全球肥胖人数达11.3亿

[3]

。同时《中国居民营养与慢性病状况报告（2020年）》显示我国超重/肥胖人群超过50%，6-17岁、6岁以下儿童和青少年超重/肥胖率分别达到19.0%和10.4%

[4]

。从2012年至今，全球癌症患者患癌的病因中6%归因于超重或肥胖和2型糖尿病。同时肥胖和2型糖尿病的高发进一步加剧其他癌症的形成

[5]

。多项研究表明运动结合药物可逆转肥胖产生的危害作用。纳西族药青刺尖显著降低肥胖小鼠血浆TG（甘油三酯）、TC（胆固醇）和LDL-C（低密度脂蛋白）水平，显著升高HDL-C（高密度脂蛋白）、LPL（脂蛋白脂肪酶）和PL（血磷脂）蛋白表达，从而改善肥胖小鼠脂肪细胞肥大和脂质沉积，降低血脂抑制肥胖的形成

[6]

。同时急性抗阻运动和急性耐力结合高剂量二甲双胍显著改善2型糖尿病的血糖稳态和抑制肝脏糖异生

[7]

。基于此，本文主要阐述运动结合药物对肥胖和2型糖尿病中脂肪因子，如瘦素和脂联素以及TGF-β/Smad2/3和AMPK/UCP1信号通路蛋白表达的调控作用。

2．方法

2.1．瘦素

人体脂肪组织主要分为白色脂肪、棕色脂肪和米色脂肪。瘦素主要是由白色脂肪分泌的一种激素，对物质代谢、生长发育以及能量稳态的调控都有重要的作用。瘦素受体是由下丘脑分泌的，通常存在于骨骼肌和脂肪组织中。瘦素介导的信号传导通路与脂代谢息息相关，外周组织如骨骼肌、肝脏和脂肪组织的脂代谢主要通过AMPK和SCD1（stearoyl-CoA desaturase-1，硬脂酰辅酶A去饱和酶1）信号通路发挥作用

[8]

。瘦素需与瘦素受体结合才能发挥生物学功能，当瘦素受体功能障碍时会影响脂肪组织的内分泌功能，促进人体膳食摄入增加和脂肪堆积，进而诱导肥胖、2型糖尿病等慢性病的形成。瘦素在调控脂代谢方面受到药物、运动、膳食等多方面因素的影响，本文将分别阐述其单个因素的作用和多个因素的联合作用。

2.1.1．抗精神类药物调控瘦素介导的脂代谢

经常使用抗精神类药物诱导和加速人体糖脂代谢紊乱，从而加剧肥胖的发生。瘦素由脂肪和骨骼肌组织分泌释放，与瘦素受体结合进入血液中，通过血脑屏障与下丘脑等与长型瘦素受体（LepRb，long isoform of the leptin rceptor）结合激活JAK2/STAT3（Janus激酶2/信号转导因子和转录激活因子3）信号通路，促进外周组织对游离脂肪酸的利用，减少脂肪堆积，抑制脂肪合成，抑制肥胖形成和发展

[9]

。经常使用抗精神类药物会干扰瘦素的转运环节，使得奥氮平和催乳素等基因表达增多，从而促进食欲和增加脂肪堆积，加速脂肪合成，造成糖脂代谢紊乱，进一步加剧肥胖的发生。肥胖人群自身ob/ob基因转录水平较高，促使瘦素蛋白表达显著增加，而由于机体多余的瘦素堆积促使瘦素抵抗的形成，进一步加剧和恶化肥胖

[10]

。

2.1.2．运动调控瘦素介导的脂代谢

研究表明20周耐力运动训练显著降低成年男性和女性的血浆瘦素水平，同时长期耐力运动训练对人体血糖、血脂和骨骼肌中脂肪酸氧化都有促进作用

[11]

。长期耐力运动训练促进人体相对最大摄氧量的升高，同时增强机体物质代谢和能量消耗。耐力运动也称为有氧运动，相比于无氧运动，有氧运动是调动机体的全身性运动，促进全身血液循环和心血管系统的功能，增加神经系统和运动系统的兴奋性，离不开消化系统、内分泌系统和免疫系统的协同作用。动物实验研究表明经过9周有氧耐力训练后，相比于久坐型小鼠，运动型小鼠的体重显著下降约10%，血浆瘦素（leptin）水平和甘油三酯（triglycerides，TG）含量显著降低。而人体实验表明经过有氧耐力运动训练的人具有更强的脂肪酸氧化能力

[12]

。AMPK是AMP激活的蛋白激酶，由α亚基、β亚基、γ亚基组成，其中α亚基分为α1和α2亚基，β亚基分为β1和β2亚基，γ亚基分为γ1、γ2和γ3亚基。AMPK的激活受上游激酶LKB1和CaMKKII、运动、药物等因素的作用，同时AMPKα Thr172磷酸化位点的激活促进线粒体中脂肪酸氧化分解。AMPK是机体不同器官和组织中重要的能量感受器，对骨骼肌和脂肪组织的能量代谢起到重要的调控作用，促进糖和脂肪的有氧氧化，抑制糖异生作用和脂肪合成

[13]

。骨骼肌细胞核中PGC-1α DNA基因表达增强，促进肌细胞线粒体中脂肪酸β-氧化和ATP的生成，进而增加线粒体的产热作用。有氧/耐力运动激活AMPK调控的信号通路，同时运动上调PGC-1α基因表达，因为运动情况下AMPK激活PCG-1α，加强骨骼肌脂肪酸氧化能力

[14, 15]

。

研究表明肥胖人群表现为瘦素抵抗，有氧耐力运动训练可显著增加血浆、肌肉和脂肪组织中瘦素表达水平，显著降低不同组织中TG含量。吴菊花等人研究发现，低氧环境结合耐力训练可通过增加HIF-1α（低氧诱导因子-1氧）蛋白表达促进瘦素基因的转录过程，促使瘦素分泌增加，从而达到减肥的效果

[16]

。因而，这些研究表明运动，尤其是有氧耐力运动激活AMPK调控的信号通路，增加PCG-1α mRNA表达，从而促进脂肪分解，抑制糖和脂肪的合成，使肥胖人群的血糖、血脂稳态重新达到平衡。

2.1.3．运动结合药物对瘦素介导脂代谢的影响

长期有氧耐力运动训练结合二甲双胍削弱2型糖尿病大鼠糖脂代谢紊乱和降低其脂肪含量，同时增加骨骼肌瘦素水平，进一步缓解2型糖尿病大鼠瘦素抵抗现象

[17]

。其他研究表明有氧运动和饮食干预后血清/血浆脂肪酸、棕榈酸和类固醇，包括TC（血浆胆固醇）、TG（血浆甘油三酯）、LDL-C（血浆低密度脂蛋白）等指标呈下降趋势，二者联合作用调节并降低体脂百分比和减重的作用；同时抑制糖原分解，降低血糖水平，同时提高胰岛素的敏感性

[18]

。急性运动对机体瘦素表达水平的影响不明显，但是长时间有氧运动训练会显著降低成年人血浆瘦素水平，从而降低其体脂含量

[11]

。研究表明在经过运动和饮食的干预后，TG、TC、瘦素的水平都呈现下降趋势，削弱肥胖患者瘦素抵抗现象，增加瘦素分泌和提高瘦素受体（leptin receptor）敏感性

[18]

。

2.2．脂联素

脂联素由脂肪细胞分泌，包括白色脂肪细胞和棕色脂肪细胞，对糖脂代谢紊乱、肥胖、2型糖尿病、动脉粥样硬化等代谢性疾病发挥重要的调控作用。脂联素与脂联素受体相结合通过激活AMPK、PPARα等分子介导的信号通路调控机体脂代谢，脂联素受体主要包含两种亚型1型和2型，1型分布于骨骼肌和2型分布于肝脏中

[19]

。同时脂联素通过抑制p70S6激酶的活性增加胰岛素敏感性，从而促进葡萄糖摄取和脂肪酸氧化

[20]

。2型糖尿病和肥胖人群脂联素表达水平呈现下降趋势，脂联素表达降低抑制脂肪酸β-氧化，促进脂肪合成，最终导致肥胖

[21]

。

2.2.1．药物和饮食干预对脂联素的调控作用

抗精神类药物过量使用显著抑制脂联素生物活性与分泌，激活JNK1/2蛋白表达及活性、抑制AMPK/ACC及AMPK/PPARα等信号通路的蛋白活性，显著抑制脂肪酸氧化，促进脂肪合成，进而诱发肥胖、糖尿病和炎症反应。饮食干预对脂联素呈双向调控作用：过量饮酒、吸烟、频繁外出就餐及高脂膳食显著降低脂联素水平，加剧脂代谢紊乱；而低脂饮食、地中海饮食、增加深黄色蔬菜摄入及减少吸烟和外出就餐，促进脂联素分泌。禁食、肥胖等状态还通过影响UGT、CYP3A4等药物代谢酶间接改变药物动力学与脂联素水平。总体而言，药物和不良的饮食习惯抑制脂联素分泌，健康饮食促进其分泌，二者共同影响脂肪分解和脂肪合成过程，而运动可反向改善这些信号通路，进而抑制肥胖的形成。

2.2.2．抗精神类药物调控脂联素分泌

抗精神类药物的过量使用会造成体内代谢紊乱，促使脂肪合成增加，减少脂肪分解，从而导致肥胖。并且长期使用抗精神类药物会造成胰岛素抵抗和瘦素抵抗

[22]

。作为MAPK（mitogen-activated protein kinase，促分裂原活化蛋白激酶）亚家族的JNK（c-Jun N-terminal kinase，c-Jun氨基末端激酶）蛋白，JNK信号通路的激活抑制Akt介导的胰岛素信号通路，促进AP-1（activator protein-1，激活蛋白1）和NF-κB（nuclear factor-κB，核因子-κB）分泌，导致游离脂肪酸、TNFα、IL-6等炎症因子分泌增加，进而加速胰岛素抵抗的形成

[23]

。研究表明JNK基因敲除会减轻炎症反应和胰岛素抵抗，因为肥胖诱导的炎症和FFA（游离脂肪酸）会激活JNK在丝氨酸或苏氨酸胰岛素受体底物1和2的磷酸化以及IRS-Tyr的去磷酸化，抑制IRS（胰岛素受体底物）激活PI3K。PI3K/Akt信号通路受阻后，胰岛素敏感性降低，最终导致胰岛B细胞凋亡和2型糖尿病的形成

[23]

。同时Yang等人研究发现高脂膳食喂养且JNK基因敲除的小鼠胰岛素抵抗现象显著削弱，肥胖小鼠糖脂代谢能力显著提高

[24]

。大量使用抗精神病类药物后，造成食欲上涨，降低脂联素分泌和促进炎症反应，加速肥胖形成与发展。脂联素通过促进脂肪酸氧化降低FFAs（free fatty acids，游离脂肪酸）含量，在与受体的结合下，激活AMPK/ACC（acetyl CoA carboxylase，乙酰辅酶A羧化酶）信号通路，使其磷酸化；同时脂联素可激活PPARα（过氧化物酶体增值物）信号通路，而PPARα下游有更多让脂肪酸氧化分子如CPT1/2（carnitine palmitoyltransferase I/II，肉毒碱棕榈酰转移酶1/2）、FABP3（fatty acid binding protein 3，脂肪酸结合蛋白3）等。相比于AMPK/PPARα对脂代谢的调控作用，AMPK/ACC信号对脂肪酸氧化的调控作用更持久

[25]

。一些研究表明氯氮平、奥氮平等抗精神病类药物抑制脂联素的生物活性

[19]

。这表明降低脂联素的分泌抑制组织脂肪酸氧化，促进脂肪合成，从而导致一系列代谢类疾病的发生。总而言之，抗精神病药物的过量使用使脂联素分泌减少，导致肥胖和炎症反应的发生，可能通过调控AMPK/ACC、AMPK/PPARα、JNK等信号通路的活性发挥作用，进而抑制脂肪酸氧化，促进脂肪合成代谢，而运动可能反向影响这些信号通路，从而改善肥胖人群脂代谢和血脂稳态。

2.2.3．饮食干预调控脂联素分泌

不同的饮食习惯对脂联素的分泌产生不同的效果。研究表明适当饮酒会增加胰岛素分泌。但过量饮酒会造成酒精性脂肪肝，导致脂联素分泌减少

[19, 26]

。禁食期间ATGL（adipose triglyceride lipase，脂肪组织甘油三酯脂肪酶）蛋白表达显著上升，G0S2（G(0)/G(1) Switch Gene 2）是ATGL抑制剂蛋白，由103个氨基酸编码的小分子蛋白，G0S2主要作用于脂肪组织，抑制脂肪细胞生长和分化，相反的运动抑制ATGL蛋白表达，促进G0S2蛋白表达

[27]

。同时其他研究表明短期禁食结合高脂膳食可促进细胞色素UGT（UDP-glucuronosyl transferase，尿苷二磷酸葡萄糖醛酸转移酶）和CYP3A4（细胞色素酶）介导的药物代谢。而UGT是人体重要的代谢酶，可催化许多内源性物质像雌激素、胆汁酸等物质，也能终止内源性激素信号防治肿瘤的发生，当然在特定情况下内源性物质也可抑制UGT的活性

[28]

。CYP3A4也是人体重要的酶，属于p450家族，可氧化外源的有机小分子像毒素或药物，主要分布在肝脏和小肠中。通过营养状况影响p450蛋白活性，进而改变药代动力学。肥胖和禁食诱导脂肪变性导致小鼠肝脏UGT蛋白表达上升

[29]

。研究表明多次外出吃饭、吸烟减少血浆脂联素分泌，而多吃深黄色蔬菜促进血浆脂联素的分泌，因而患有高血糖、高血脂的日本男性若减少吸烟量和外出吃饭次数可有效促进脂联素分泌，降低高血脂的形成。并且低脂饮食和地中海饮食都会显著增加脂联素分泌

[30]

。经常服用抗精神类药物和过量饮酒以及吸烟等习惯导致脂联素分泌不足，抑制脂解作用，促进脂肪合成，加速肥胖的形成。

2.2.4．运动调控脂联素分泌

运动可改变体内的脂肪酸含量。让甘油三酯水解为脂肪酸，利用肌肉脂肪的水解产物脂肪酸消耗热量。同时在急性运动中往往先以糖类物质来补充能量，而在长跑运动中以脂肪酸的氧化来补充能量。运动离不开骨骼肌收缩和舒张，能量供应主要来自糖和脂肪的有氧氧化

[31]

。同时郭吟等人研究表明经过长期的有氧运动训练显著增加骨骼肌葡萄糖转运和利用能力，从而降低血糖水平。与此同时，长期有氧耐力运动训练提高胰岛素敏感性进而缓解胰岛素抵抗

[18]

。AMPK作为经典的能量感受器，在运动的刺激下，PGC-1α表达上升可增加脂肪酸的氧化促进骨骼肌线粒体生物发生，增加脂肪酸β肪氧化

[16]

。9周有氧运动训练使小鼠体重下降约10%，同时诱导瘦素、TCIA（transient cerebral ischemic attacks，短暂性大脑缺血性发作）、甘油三酯等因子的下降。并且耐力运动促使摄食量减少、脂解作用加强，从而促进脂联素分泌和抑制肥胖的发生

[12]

。关于运动上调脂联素表达水平的研究结果也有矛盾的地方，有氧耐力运动有效降低肥胖青少年的血脂和增加血清脂联素水平。但其他研究表明运动后血清脂联素水平下降，运动不能有效增加血清脂联素水平，但体脂含量的增加可促进血清脂联素水平的增加，导致这种结果的原因可能与自身超重引起的机体变化有关

[32]

。类似的研究表明8周中等强度的跑台运动训练促进白色脂肪组织中鸢尾素（Irisin）蛋白的表达，进而促进FNDC5/Irisin蛋白介导的白色脂肪组织向棕色脂肪组织转变，即白色脂肪组织棕色化；同时运动显著增加肌肉组织FNDC5/Irisin和UCP1蛋白表达，促进线粒体产热作用和脂肪酸氧化

[33]

。研究表明低强度或中等强度有氧运动通过促进AMPK/SIRT1信号通路的蛋白表达，促进PPARα蛋白表达，从而促进脂肪酸氧化能力

[34]

。长期有氧运动导致脂联素表达增加，脂联素表达水平升高促进脂肪分解作用，进而抑制肥胖的形成。

2.2.5．运动结合饮食干预调控脂联素分泌

单纯运动和低脂饮食都显著促进脂肪分解和脂代谢。其他研究表明运动和饮食干预的结合产生的作用效果比单个干预因素产生的效果更好。在运动和饮食干预的结合的研究中发现，血清TG和TC表达水平都下降，有氧运动促进脂联素（adiponectin）和AMPK蛋白表达，同时促进AMPK磷酸化，增加线粒体氧化磷酸化功能和脂肪酸β氧化，从而达到改善血脂和减轻体重的效果。但是高脂膳食使肌肉组织AMPK活性降低以及AMPK介导的信号通路失活，但长期中高强度有氧运动训练激活AMPK及其调控的分子信号通路

[35]

。同时运动结合饮食干预有效改善肥胖患者/啮齿类动物体脂含量，研究表明FNDC5/Irisin（纤维连结蛋白III型域包含蛋白5，鸢尾素）促进白色脂肪组织向棕/褐色脂肪组织转变，即白色脂肪组织棕色化，从而促进能量消耗。研究表明4周跑台运动结合饮食干预显著降低肥胖小鼠附睾白色脂肪组织和肾周白色脂肪组织含量；同时棕色脂肪也出现下降可能与快速减重的结果相关

[36]

。运动激活AMPK，同时PGC-1α作为下游也被激活，AMPK/PGC-1α信号通路和能量摄入限制可上调FNDC5蛋白表达，同时饮食热量限制结合运动更好地发挥减脂作用

[37]

。同时发现大鼠肾周白色脂肪组织中UCP1蛋白表达水平显著增加，PGC-1α促FNDC5表达并释放Irisin调控UCP1，增加线粒体产热效果，促进白色脂肪组织棕色化，进而加速能量代谢

[38, 39]

。另一项研究表明运动显著增加腹股沟白色脂肪组织UCP1蛋白表达，UCP1 mRNA转录水平随运动强度的增加而增加

[40]

。

在饮食和运动的双重干预下，肥胖小鼠中脂联素、AMPK、LKB1、APPL1表达为上升趋势，通过APPL1-LKB1-AMPK信号通路促进脂质代谢，降低血浆/血清TG（甘油三酯）、肝脏组织FFA（游离脂肪酸）和ACC（乙酰辅酶A羧化酶）酶的活性，改善机体糖、脂代谢紊乱

[20]

。研究表明低脂饮食结合运动改善肥胖引起的炎症反应，表现为IL-6、TNF-α等标志性的炎症因子表达下降，进而改善肥胖人群的炎症反应和身体素质

[41]

。综上所述，运动结合饮食干预促进脂联素和ATGL（脂肪组织甘油三酯脂肪酶）蛋白表达，降低血浆/血清TG、TC和FFA含量，可有效激活AMPK及其介导的分子信号通路，增强脂肪组织的脂解作用，促进白色/棕色脂肪组织UCP1、CPT1/2和PGC-1α基因和蛋白表达，而一些研究表明单纯运动或低脂饮食干预比二者结合的效果更好，这种差异性背后具体的细胞分子机制仍有待进一步研究。

3．结果

3.1．药物对TGF-β信号通路的影响

TGF-β1是TGF-β 超家族的重要成员，在肥胖、2型糖尿病等代谢类疾病中发挥重要作用。TGF-重家族受体之一ALK7（Activin receptor-like kinase 7，活化素受体样激酶7），新的研究发现除了常见的ALK4、ALK5受体，ALK7抑制剂或ALK7基因敲除促进白色脂肪组织瘦素和脂联素的分泌，进而对肥胖、2型糖尿病等代谢类疾病具有治疗作用，同时ALK7也具有调控免疫应答反应、胰岛组织胰岛素分泌功能和肌肉功能的作用

[42]

。TGF-β大家族由35个配体和12个受体组成，其家族成员有典型的结构组织，形成两个由120个氨基酸残基组成的多肽链组成的同源或异源二聚体，它们本身是由一个更大的前体蛋白水解而产生

[43]

。研究表明PUR（Puerarin，葛根素）对2型糖尿病、心血管疾病和NAFLD（non-alchoholic fatty liver disease，非酒精性脂肪肝）代谢类疾病具有改善作用。在高脂膳食和STZ联合诱导的2型糖尿病大鼠中，葛根素通过抑制TGF-β/Smad和NF-κB信号通路，降低2型糖尿病大鼠肝脏组织氧化应激和抑制其炎症反应，减少肝脏组织纤维化，同时葛根素通过抑制2型糖尿病大鼠肝细胞TGF-β/Smad3信号通路降低肝脏脂肪合成

[44]

。高尿酸血症（hyperuricemia，HUA）是导致慢性肾病的重要病因，诱导肾小管纤维化和肾脏脂肪酸氧化不足。ZQTF（滋肾清热通络方）是中国古代草本药物，可有效治疗痛风。研究发现滋肾清热通络方通过抑制TGF-β/Smad2/3信号通路蛋白磷酸化，激活PGC-1α、PPARγ和PPARα表达，降低肾脏组织和细胞甘油三酯水平以促进其脂肪酸氧化，降低高尿酸血症大鼠血清尿酸水平，从而改善高尿酸血症肾病、肾脏组织纤维化、肺间质纤维化和肝脏组织纤维化

[45]

。

3.2．运动对TGF-β信号通路的影响

肝脏纤维化是由慢性病肝损伤诱导的细胞外基质（ECM，extracellular matrix）积累，基于KD（ketogenic diet，生酮饮食）造模的2型糖尿病小鼠，其血清缺氧诱导因子-1α（HIF-1α）表达水平较高，氧化应激作用增强，导致TGF-β表达水平上升。HIIT（high intensity interval training，高强度间歇运动训练）是有别于中等强度持续性训练，前者更易激活AMPK调控的GLUT4（glucose transporter 4，葡萄糖转运蛋白4）转位至肌细胞膜，从而促进机体糖代谢。研究表明8周HIIT抑制2型糖尿病小鼠肝脏组织TGF-β/Smad2/3信号通路蛋白表达，减少ROS（reactive oxygen species，氧自由基）的生成，进而改善KD诱导的肝脂肪变性和肝脏纤维化

[46]

。在STZ（streptozotocin，链脲佐菌素）结合高脂膳食诱导2型糖尿病大鼠的模型中，心肌衰竭和心肌功能障碍诱导TGF-β1蛋白表达升高。TGF-β1/Smad2/3信号通路的激活表现在通过调控Smad2/3蛋白表达，Smad2、Smad3被磷酸化，Smad7上调，该通路激活TIMP-1蛋白活性，降低MMP-2蛋白表达，而MMP-2与TIMP蛋白表达的失衡可能导致心肌衰竭。长期的运动训练减少糖尿病组小鼠ROS形成，有效抑制TGF-β信号通路，降低心肌衰竭和心功能障碍

[47]

。规律的体育锻炼增加人体健康体适能，体适能的增强抑制ROS的生成，从而降低机体系统、器官和组织氧化应激反应。研究表明经常从事自行车运动的人和静坐少动者，他们的空腹血糖水平（FBP，fasting blood glucose）无显著性差异，但自行车运动爱好者的脂质谱（lipid profile）优于静坐少动者，并且他们的TGF-β平均值显著低于静坐少动者。研究表明TGF-β参与脂质发育，同时TGF-β水平与肥胖、超重、BMI等指标显著相关。TGF-β1可以通过诱导NADPH氧化酶，抑制抗氧化酶活性，增加不同类型细胞中线粒体ROS生成，导致线粒体电子传递链氧化还原反应失衡；有规律的体育锻炼减少ROS生成，TGF-β1蛋白表达水平较低

[48]

。综上所述，不同的运动方式对TGF-β表达水平的影响是不同的，可能受炎症和心肌纤维化诱导的线粒体ROS变化等方面的影响。基于此，需要采用不同的运动项目研究对机体TGF-β蛋白表达的影响，从而改善机体糖脂代谢及其相关细胞分子机制。

3.3．运动结合药物干预对TGF-β信号通路的影响

VD₃（维生素D₃）是含有多种生物学效应的类固醇激素，通过与维生素D受体结合，增加PPARα、PPAR激蛋白表达，降低血浆甘油三酯水平以减少脂质堆积，同时心肌细胞含有大量的维生素D受体，VD₃与维生素D受体结合发挥作用后，抑制病理性的心肌肥大，同时升高PPAR性蛋白表达

[49]

。VD₃被证明可改善癌症和2型糖尿病，但对心血管疾病作用的分子机制尚未明确。心血管疾病表现为心肌纤维化，其中胶质蛋白、TGF-β表达增多，诱导Smad3/4磷酸化促进调控心肌纤维化的因子蛋白表达。同时TGF-β、Smad3与心肌氧化应激水平和胶质蛋白增多有关，TGF-β表达升高促进ROS诱导的心肌梗死（MI，myocardial infarction）

[50]

。而VD₃通过抑制NADPH（还原型辅酶Ⅱ）酶的活性下调肾素-血管紧张素-醛固酮的分泌，从而减少ROS生成。且肾素-血管紧张素-醛固酮的上升会增加TGF-β蛋白表达，促进心肌纤维化进一步恶化

[51, 52]

。在VD₃结合ARET（aerobic and resistance exercise training，有氧结合抗阻训练）通过显著降低TGF-β和Smad2/3蛋白磷酸化水平抑制胶质细胞脂质积累和心肌纤维化，从而增加运动能力。有氧结合抗阻训练，同时补充VD₃可显著增加MI大鼠心房和心室重量，提高MI大鼠心脏射血分数和心脏功能

[52, 53]

。研究表明VD₃结合有氧+抗阻运动训练可有效改善心肌纤维化和抑制炎症反应，减少脂质堆积，对心脏病、心肌纤维化、心肌梗死等心血管疾病具有良好的疗效。

AMPK是感知能量代谢的细胞感受器，由α亚基、β亚基和γ亚基组成，在葡萄糖浓度降低或缺乏、[AMP]/[ATP]比值升高和运动的条件下促进AMPK的激活，参与调节糖脂代谢、癌症、NAFLD（non-alcoholic fatty liver disease，非酒精性脂肪肝）等疾病机制

[54]

。LKB1是一种抑制肿瘤基因丝氨酸/苏氨酸激酶，是AMPK的上游激酶，促进LKB1/AMPK信号通路蛋白表达，诱导AMPK Thr172位点磷酸化；LKB1基因敲除抑制AMPK Thr172位点磷酸化，从而使机体血糖和血脂升高，导致糖脂代谢紊乱

[55, 56]

。作为AMPK下游效应物ACC，ACC是脂肪酸合成的限速酶，对脂肪合成具有重要的促进作用。研究表明苯丙氨酸通过L型氨基酸转运体（LAT1，L-type amino transporters）摄取增加，进而激活LKB1/AMPK信号通路，该信号通路上调过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）和Bcl-2/Bax比值，同时抑制解偶联蛋白2（UCP2）蛋白表达，进而改善低氧环境中线粒体功能

[57]

，从而改善能量代谢和细胞生存能力。因不同的运动方式对AMPK及其相关信号通路的促进效果不同，同时AMPK作为骨骼肌能量感受器

[54]

，在低氧运动下促进AMPK表达，会诱导PGC-1α蛋白表达，促进线粒体生物发生和脂肪酸β氧化

[16]

。2型糖尿病中，AMPK促进PGC-1α蛋白表达，诱导PPARα蛋白表达升高，促进脂解作用和改善脂肪细胞脂毒性和炎症反应，从而改善2型糖尿病

[58]

。而且AMPK可能是TGF-β1和Smad2/3蛋白的上游激酶，在调控肥胖和2型糖尿病中起到重要的促进作用。IQ（槲皮素）是一种葡萄糖苷衍生物，可减弱NAFLD引发的不利作用。IQ抑制高脂膳食喂养的大鼠TGF-β和Smad3蛋白磷酸化，减少脂肪合成。同时IQ激活AMPK诱导KCs细胞增加，通过TGF-β受体和Smad2/3抑制TGF-β的表达

[59]

。反之，TGF-β抑制AMPK Thr172位点磷酸化，同时加速肾脏纤维化

[60]

。研究表明AMPK上调Smad6蛋白表达，但其对Smad信号通路是抑制作用；且AMPK可以抑制TGF-β带来的MIT，表明AMPK负调控TGF-β表达水平。AMPK的激活抑制TGF-β转录水平，从而减少Smad2/3蛋白表达和磷酸化，降低脂质积累和削弱心肌纤维化

[61-63]

。在补充VD₃和有氧抗阻运动训练、AMPK相关信号通路的激活会抑制TGF-β蛋白表达，降低Smad2/3磷酸化，从而改善心肌梗死、心肌纤维化等心血管疾病、肥胖和2型糖尿病引起的糖脂代谢紊乱。

4．讨论

4.1．药物对UCP1蛋白表达的调控作用

棕色脂肪的线粒体含量和活性高，表现为棕色脂肪UCP1蛋白高表达，从而促进脂肪组织线粒体的产热作用。通过线粒体解偶联蛋白（UCPs）调控脂肪酸的氧化分解作用，为机体提供热量，从而维持人体的物质和能量平衡

[64]

。研究表明咖啡因可预防超重，长期使用咖啡因增加脂肪酸氧化，减少脂肪含量和增加胰岛素敏感性。研究发现高脂膳食喂养的小鼠中给与咖啡因促使小鼠体重显著下降，同时FNDC5、PGC-1α蛋白表达升高。咖啡因被视为系统性“线粒体网络优化器”，可以激活AMPK/SIRT1/PGC-1α信号通路、Nrf2/ARE抗氧化信号通路和PINK1/Parkin介导的线粒体自噬和线粒体钙离子信号通路，进而协同增强线粒体生物发生、质量控制、氧化还原反应和能力代谢效率

[65]

。研究表明8周高强度间歇静力性力量训练改善老年大鼠肌肉萎缩现象和运动功能，通过激活PGC-1α/FNDC5/UCP1信号通路

[66]

。大蒜油是有机化合物，具有抗生素、抗血脂、抗氧化剂、抗高血压等功效，同时大蒜有凝血功能、脂质代谢、免疫功能和异种生物代谢。大蒜粉和大蒜提取物对肥胖模型具有抗肥胖作用，大蒜包含DATS、DAS等物质，可以抑制体外脂肪的形成。DATS已被证明可以下调CCAAT/增强子结合蛋白(C/EBP)α和β以及过氧化物酶体增殖物激活受体PPARγ，导致3T3-L1脂肪细胞中脂肪酸合酶和脂质积累的减少。研究表明小鼠补充大蒜油（GO）中可减轻体重和白色脂肪组织含量，GO激活TRPA1和TRPV1，通过去加肾上腺素和β-肾上腺素信号通路上调UCP1表达。黑暗环境中长期服用大蒜油的小鼠能量消耗显著增多，脂肪酸氧化能力增强促使体重降低

[67]

。在不影响食物摄入量、身体组成成分和能量消耗的情况下，9周槲皮素治疗可显著降低血浆甘油三酯和胆固醇含量，显著升高sWAT（subcutaneous white adipose tissue，皮下白色脂肪组织）中UCP1蛋白高表达，可能通过激活AMPK/SIRT1/PGC1α信号通路，诱导白色脂肪组织棕色化，显著增加ACC磷酸化水平进而抑制脂肪合成

[68]

。先前研究表明亚洲菊提取物可逆转肥胖2型糖尿病大鼠血浆脂质水平，菜豆苷（Linamarin，C₁₀H₁₇NO₆）是从亚洲菜中提取的一种五环三萜皂苷，具有多种药用活性。8周菜豆苷治疗显著降低2型糖尿病小鼠甘油三酯等血脂水平，未显著改善2型糖尿病小鼠血糖水平，分子作用机制可能通过激活AMPK/HSL信号通路上调SIRT1蛋白表达，促进附睾白色脂肪组织的脂肪分解过程。在肠系膜中通过SIRT1/AMPK/ACC抑制脂质合成，增加线粒体UCP1蛋白表达，促进白色脂肪组织褐变/棕色化和增加线粒体的产热作用

[69]

。咖啡因、菜豆苷和大蒜油通过激活像AMPK、C/EBP（α和β）等相关信号通路，增加脂解调控因子的蛋白表达，如CPT1/2、PGC-1α、UCP1等蛋白，促进白色脂肪组织棕色化和脂解作用，改善脂代谢紊乱和抑制肥胖形成与发展。

4.2．运动对UCP1蛋白表达的调控作用

运动是良好的健身方式。因为体育锻炼会增强脂肪酸氧化的表达。适当的体育锻炼会增强脂肪代谢，增加棕色脂肪组织（brown adipose tissue，BAT）的产热能力

[70]

。运动诱导肌肉收缩会增加FNDC5表达，而FNDC5是由PCG-1控制的慢性运动，两者表达上升会引起能量消耗和促进白色脂肪的褐变，显著改善糖脂代谢

[71]

。研究表明短时运动显著增加UCP1蛋白表达，因为运动刺激交感神经使其兴奋，运动促进肌肉收缩与舒张，增加机体核心温度，所以显著增加棕色脂肪组织UCP1蛋白表达。中等强度运动刺激交感神经增加儿茶酚胺激素的分泌，包括肾上腺素和去甲肾上腺素，cAMP含量的增加激活PKA活性促进UCP1蛋白表达，增强其产热作用。去甲肾上腺素-3（β3）结合α1和α2肾上腺素能受体导致分子信号转导作用级联递增。激活BAT三个受体的活性使UCP1蛋白表达显著增加。研究表明中等强度持续性运动训练40分钟显著提高肥胖女性脂肪组织UCP1蛋白表达

[70]

。游泳运动训练也是类似的效果，长期有氧耐力运动训练使比目鱼肌中PGC-1α mRNA水平呈现上升趋势，运动显著增加比目鱼肌和腓肠肌FNDC5 mRNA表达和转录水平。PGC-1α、FNDC5蛋白表达和循环鸢尾素水平的上升促进能量消耗和白色脂肪组织棕色化，从而改善胰岛素抵抗。而游泳运动训练对血清鸢尾素水平没有显著作用，但适当增加UCP1蛋白表达

[71]

。经过一周三天每天四小时的高强度或低强度跑步训练发现，跑步并未减轻腹部白色脂肪组织含量而是减少脂肪细胞大小，高强度运动训练显著提高白色脂肪组织中UCP1蛋白表达，显著增加腹股沟白色脂肪组织线粒体数量和产热能力以及骨骼肌中成纤维细胞生长因子21（Fibroblast Growth Factor 21，FGF21）蛋白表达。运动诱导AMPK活性、线粒体数量和氧化磷酸化增加，提高细胞能量代谢，尤其增强葡萄糖代谢和促进线粒体能量转变。同时运动强度是改变骨骼肌和血液成分的重要因素。慢跑显著增加皮下白色脂肪组织中UCP1表达；高强度运动诱导白色脂肪组织棕色化、改善高脂饮食引发的肥胖、炎症和糖脂代谢紊乱等问题，同时超过乳酸阈强度的运动显著增加FNDC5蛋白表达，而中等强度运动不能显著增加FNDC5蛋白表达。四周跑步运动显著增加AMPK蛋白表达和激活AMPK下游效应物ACC，促进脂肪酸氧化。并且腹股沟白色脂肪组织UCP1蛋白表达和腓肠肌FGF21蛋白表达呈显著正相关，表明高强度运动训练促进UCP1和FGF21蛋白表达，进而促进白色脂肪组织棕色化。除此之外，四周高强度的跑步运动显著增加NDUF88和SDHB蛋白表达，促进肥胖人群脂肪组织脂解作用，高强度运动训练更能促进白色脂肪组织棕色化，有效预防肥胖

[72]

。但是其他研究表明四周有氧运动显著增加肥胖小鼠UCP1蛋白表达，但伴随时间延长，调控棕色脂肪组织生物合成和脂肪酸氧化的相关基因表达水平（mRNA水平）降低。其他研究表明有氧运动增加棕色脂肪组织UCP1蛋白表达可能不依赖于AMPK蛋白表达和激活。总之，有氧运动上调葡萄糖代谢胰岛素、AMPK等相关基因表达、脂质代谢（PPARα/P、VEGF)和下调炎症因子相关分子信号通路

[73]

。所以不同的运动方式对UCP1蛋白表达的作用是不同的，UCP1蛋白表达的高与低，可能与训练周期、小鼠身体状态等多方面因素相关。

4.3．运动结合药物干预对UCP1蛋白表达的影响

运动对健康本身就有促进作用，草本补充剂会增加锻炼的效果。UA（熊果酸，ursolic acid）是一种草本植物，具有抗肿瘤、抗炎、减肥和减脂的功效，苹果和其他草本植物化合物都含有UA，UA补充剂是增加棕色脂肪组织含量的有效方法之一。在高强度力量训练训练中发现，UA结合高强度力量训练显著增加UCP1和FNDC5蛋白表达以及显著提高血浆鸢尾素（Irisin）水平。UA补充剂的生物活性受到PI3K/Akt信号通路的影响，通过刺激UCP1保护H9C2肝细胞免受缺氧损伤。这些变化可能归因于身体情况、运动模式、训练条件等方面的变化

[74]

。红辣椒的辣椒素显著增加产热基因转录水平的表达，如PGC-1α、UCP1、PRDM-16等基因。PGC-1α会促进FNDC5表达，促进FNDC5分泌到血液中形成鸢尾素，诱导UCP1和线粒体的发生。在有氧运动结合辣椒素通过SIRT1/AMPK/PGC-1α增加鸢尾素蛋白表达，促进白色脂肪组织棕色化，抵消HFD喂养带来的副作用。运动自身促进PGC-1α表达升高，促进鸢尾素分泌；单纯豆角补充促进机体抗氧化和抗炎特性，从而降低运动引起氧化应激和炎症反应。在给予肥胖男性豆角补剂的研究中发现肥胖男性的鸢尾素表达无显著变化，长期抗阻训练和豆角补充显著增加鸢尾素水平，进而改善血脂水平

[75]

。与此同时，不是所有药物结合运动皆能带来良好的治疗效果。腺苷通过与刺激受体A2A、A2BG蛋白受体结合，增加腺苷环化酶（AC，adenylate cyclase）活性增加cAMP（环一磷酸腺苷，第二信使）含量，研究表明cAMP结合耐力运动显著降低小鼠体重和甘油三酯水平，仅有腺苷补充对UCP1蛋白表达作用较小，鸢尾素诱导UCP1和P2RX5基因（白色脂肪棕色化的关键基因）表达，同时显著调ADORA1、ADORA2A和P2RX4基因转录，鸢尾素是FNDC5蛋白剪切分泌的小分子蛋白，具有抵抗肥胖的作用

[76]

。大部分药物结合不同的运动方式对线粒体产热基因，如UCP1/2都有一定的促进作用，但结果不一致，具体细胞分子机制有待进一步研究。

5．结论

不同的运动方式（有氧耐力运动和无氧抗阻运动）结合药物可通过降低脂肪组织和骨骼肌中瘦素、脂联素水平，激活AMPK/UCP1和TGF-β/Smad2/3信号通路蛋白表达，促进白色脂肪组织棕色化和线粒体脂肪酸β氧化，从而改善肥胖、2型糖尿病等代谢类疾病糖、脂代谢紊乱，抑制疾病的形成和恶化。同时运动结合药物也可激活Akt介导的胰岛素信号通路和AMPK/ACC介导的脂肪酸氧化信号通路，这些经典的能量物质合成和分解代谢通路，从而促进PGC-1α和Irisin等蛋白表达。然而，与单独药物或运动因素对肥胖、2型糖尿病等代谢类疾病改善机体糖、脂代谢相比，运动结合药物的双因素改善糖脂代谢的作用机制更复杂，作用效果不完全明确，可能是促进作用，也可能是抑制作用，有待进一步探索与研究。这也是未来体医融合关注的重点和突破口。

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Li, F., Shen, W. (2026). The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Science Research, 14(6), 395-405. https://doi.org/10.11648/j.sr.20261406.12

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Li, F.; Shen, W. The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Sci. Res. 2026, 14(6), 395-405. doi: 10.11648/j.sr.20261406.12

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Li F, Shen W. The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Sci Res. 2026;14(6):395-405. doi: 10.11648/j.sr.20261406.12

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@article{10.11648/j.sr.20261406.12,
  author = {Fuhui Li and Wenqing Shen},
  title = {The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States},
  journal = {Science Research},
  volume = {14},
  number = {6},
  pages = {395-405},
  doi = {10.11648/j.sr.20261406.12},
  url = {https://doi.org/10.11648/j.sr.20261406.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sr.20261406.12},
  abstract = {Obesity and type 2 diabetes mellitus, as major epidemiological research topics, have become global public health concerns that profoundly impact human health. According to data from the 2025 report of the National Health Commission of China, based on body mass index (BMI) and body fat percentage measurements, the prevalence of overweight among Chinese adults reached 34.3%, while the prevalence of obesity was 16.4%, yielding a combined overweight and obesity rate of 50.7%. Chronic positive energy balance, resulting from energy intake exceeding energy expenditure, leads to disruption of energy homeostasis, thereby promoting the development of chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Among these, obesity and type 2 diabetes induce disorders of glucolipid metabolism and mitochondrial dysfunction, with lipid metabolic disturbances being the most prominent. This review primarily focuses on the effects of various exercise modalities combined with pharmacological interventions on adipokine profiles in obese patients or rodent models, as well as the roles of the TGF-β/Smad2/3 and AMPK/UCP1 signaling pathways in lipid metabolism. We conclude that the combination of exercise and drug therapy effectively suppresses adipokine secretion and inhibits TGF-β/Smad2/3 signaling, thereby attenuating lipogenesis, while concurrently activating the AMPK/UCP1 pathway to enhance lipolysis. Therefore, exercise combined with pharmacological treatment can effectively regulate adipokine secretion and modulate the TGF-β/Smad2/3 and AMPK/UCP1 signaling cascades, offering a promising strategy for the prevention and treatment of obesity and other metabolic disorders.},
 year = {2026}
}

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TY  - JOUR
T1  - The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States
AU  - Fuhui Li
AU  - Wenqing Shen
Y1  - 2026/11/10
PY  - 2026
N1  - https://doi.org/10.11648/j.sr.20261406.12
DO  - 10.11648/j.sr.20261406.12
T2  - Science Research
JF  - Science Research
JO  - Science Research
SP  - 395
EP  - 405
PB  - Science Publishing Group
SN  - 2329-0927
UR  - https://doi.org/10.11648/j.sr.20261406.12
AB  - Obesity and type 2 diabetes mellitus, as major epidemiological research topics, have become global public health concerns that profoundly impact human health. According to data from the 2025 report of the National Health Commission of China, based on body mass index (BMI) and body fat percentage measurements, the prevalence of overweight among Chinese adults reached 34.3%, while the prevalence of obesity was 16.4%, yielding a combined overweight and obesity rate of 50.7%. Chronic positive energy balance, resulting from energy intake exceeding energy expenditure, leads to disruption of energy homeostasis, thereby promoting the development of chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Among these, obesity and type 2 diabetes induce disorders of glucolipid metabolism and mitochondrial dysfunction, with lipid metabolic disturbances being the most prominent. This review primarily focuses on the effects of various exercise modalities combined with pharmacological interventions on adipokine profiles in obese patients or rodent models, as well as the roles of the TGF-β/Smad2/3 and AMPK/UCP1 signaling pathways in lipid metabolism. We conclude that the combination of exercise and drug therapy effectively suppresses adipokine secretion and inhibits TGF-β/Smad2/3 signaling, thereby attenuating lipogenesis, while concurrently activating the AMPK/UCP1 pathway to enhance lipolysis. Therefore, exercise combined with pharmacological treatment can effectively regulate adipokine secretion and modulate the TGF-β/Smad2/3 and AMPK/UCP1 signaling cascades, offering a promising strategy for the prevention and treatment of obesity and other metabolic disorders.
VL  - 14
IS  - 6
ER  -

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Fuhui Li

College of Physical Education, Anhui Normal University, Wuhu, China;Key Laboratory of Physiological and Biochemical Testing and Exercise Rehabilitation in College of Physical Education, Wuhu, China

Contact Email

http://orcid.org/0009-0004-4726-4406
Wenqing Shen

College of Physical Education, Anhui Normal University, Wuhu, China;Key Laboratory of Physiological and Biochemical Testing and Exercise Rehabilitation in College of Physical Education, Wuhu, China

Contact Email

http://orcid.org/0009-0005-4775-7267

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APA Style

Li, F., Shen, W. (2026). The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Science Research, 14(6), 395-405. https://doi.org/10.11648/j.sr.20261406.12

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ACS Style

Li, F.; Shen, W. The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Sci. Res. 2026, 14(6), 395-405. doi: 10.11648/j.sr.20261406.12

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AMA Style

Li F, Shen W. The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States. Sci Res. 2026;14(6):395-405. doi: 10.11648/j.sr.20261406.12

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@article{10.11648/j.sr.20261406.12,
  author = {Fuhui Li and Wenqing Shen},
  title = {The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States},
  journal = {Science Research},
  volume = {14},
  number = {6},
  pages = {395-405},
  doi = {10.11648/j.sr.20261406.12},
  url = {https://doi.org/10.11648/j.sr.20261406.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sr.20261406.12},
  abstract = {Obesity and type 2 diabetes mellitus, as major epidemiological research topics, have become global public health concerns that profoundly impact human health. According to data from the 2025 report of the National Health Commission of China, based on body mass index (BMI) and body fat percentage measurements, the prevalence of overweight among Chinese adults reached 34.3%, while the prevalence of obesity was 16.4%, yielding a combined overweight and obesity rate of 50.7%. Chronic positive energy balance, resulting from energy intake exceeding energy expenditure, leads to disruption of energy homeostasis, thereby promoting the development of chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Among these, obesity and type 2 diabetes induce disorders of glucolipid metabolism and mitochondrial dysfunction, with lipid metabolic disturbances being the most prominent. This review primarily focuses on the effects of various exercise modalities combined with pharmacological interventions on adipokine profiles in obese patients or rodent models, as well as the roles of the TGF-β/Smad2/3 and AMPK/UCP1 signaling pathways in lipid metabolism. We conclude that the combination of exercise and drug therapy effectively suppresses adipokine secretion and inhibits TGF-β/Smad2/3 signaling, thereby attenuating lipogenesis, while concurrently activating the AMPK/UCP1 pathway to enhance lipolysis. Therefore, exercise combined with pharmacological treatment can effectively regulate adipokine secretion and modulate the TGF-β/Smad2/3 and AMPK/UCP1 signaling cascades, offering a promising strategy for the prevention and treatment of obesity and other metabolic disorders.},
 year = {2026}
}

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TY  - JOUR
T1  - The Mechanism by Which Combined Exercise and Drug Therapy Modulate TGF-β/Smad2/3-regulated Lipolysis in Obese States
AU  - Fuhui Li
AU  - Wenqing Shen
Y1  - 2026/11/10
PY  - 2026
N1  - https://doi.org/10.11648/j.sr.20261406.12
DO  - 10.11648/j.sr.20261406.12
T2  - Science Research
JF  - Science Research
JO  - Science Research
SP  - 395
EP  - 405
PB  - Science Publishing Group
SN  - 2329-0927
UR  - https://doi.org/10.11648/j.sr.20261406.12
AB  - Obesity and type 2 diabetes mellitus, as major epidemiological research topics, have become global public health concerns that profoundly impact human health. According to data from the 2025 report of the National Health Commission of China, based on body mass index (BMI) and body fat percentage measurements, the prevalence of overweight among Chinese adults reached 34.3%, while the prevalence of obesity was 16.4%, yielding a combined overweight and obesity rate of 50.7%. Chronic positive energy balance, resulting from energy intake exceeding energy expenditure, leads to disruption of energy homeostasis, thereby promoting the development of chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and cancer. Among these, obesity and type 2 diabetes induce disorders of glucolipid metabolism and mitochondrial dysfunction, with lipid metabolic disturbances being the most prominent. This review primarily focuses on the effects of various exercise modalities combined with pharmacological interventions on adipokine profiles in obese patients or rodent models, as well as the roles of the TGF-β/Smad2/3 and AMPK/UCP1 signaling pathways in lipid metabolism. We conclude that the combination of exercise and drug therapy effectively suppresses adipokine secretion and inhibits TGF-β/Smad2/3 signaling, thereby attenuating lipogenesis, while concurrently activating the AMPK/UCP1 pathway to enhance lipolysis. Therefore, exercise combined with pharmacological treatment can effectively regulate adipokine secretion and modulate the TGF-β/Smad2/3 and AMPK/UCP1 signaling cascades, offering a promising strategy for the prevention and treatment of obesity and other metabolic disorders.
VL  - 14
IS  - 6
ER  -

Copy | Download