Pathogenic analysis of post-transplantation obesity: A comprehensive systematic review

Abstract

BACKGROUND

Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure, yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae, with obesity emerging as a critical clinical challenge.

AIM

To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological, behavioral, and molecular perspectives, thereby providing a foundation for targeted interventions.

METHODS

We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025. The search strategy incorporated terms including “obesity”, “overweight” and “post organ transplantation”. Only randomized controlled trials, meta-analyses, and systematic reviews were included. Non-empirical publications and irrelevant studies were excluded. Data extraction and quality assessment were performed by two independent reviewers, with disagreements resolved by a third researcher.

RESULTS

A total of 1457 articles were initially identified, of which 146 met the inclusion criteria. These studies encompassed liver, kidney, heart, and lung transplant recipients. Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia, insulin resistance, and dyslipidemia. Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance. At the molecular level, immunosuppressants disrupt adipokine signaling (e.g., leptin and adiponectin), induce inflammatory and oxidative stress responses, and activate adipogenic pathways leading to lipid accumulation.

CONCLUSION

Post-transplant obesity arises from a complex interplay of pharmacological, behavioral, and molecular factors. A multidisciplinary approach-incorporating pharmacological modification, nutritional management, physical activity, and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes. Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.

Key Words: Organ transplantation; Obesity; Metabolic dysregulation; Immunopharmacology; Adipokine dysregulation axis; Inflammation-oxidation-adipogenesis loop

Core Tip: Organ transplantation for end-stage failure faces post-transplant obesity, a key challenge. This review analyzes its multifactorial causes: Immunosuppressants (corticosteroids, calcineurin inhibitors) disrupt metabolism, hypoactivity worsens energy imbalance, poor diet promotes weight gain, and molecularly, immunosuppressants affect adipokines and insulin, with inflammation driving lipid accumulation. It offers a framework for mitigation strategies.

INTRODUCTION

Organ transplantation has become a pivotal therapeutic approach for end-stage organ failure. With advancements in surgical techniques, immunosuppressive regimens, and organ allocation systems, the global volume of transplants continues to rise[1]. Transplantation significantly improves prognosis in patients with end-stage cardiac, hepatic, and renal diseases[2,3]. However, post-transplant metabolic complications-including hypertension, diabetes, and obesity-adversely affect long-term patient health and graft survival[4,5]. These interrelated metabolic disturbances elevate cardiovascular risks and compromise therapeutic outcomes and quality of life[6,7].

Post-transplant obesity represents a prominent metabolic concern, exhibiting high prevalence across various transplant types. For instance, obesity occurs in 14% of lung transplant recipients, with overweight individuals and chronic obstructive pulmonary disease patients at particularly elevated risk[8]. Obesity not only promotes pathological fat accumulation but also triggers inflammatory responses, insulin resistance (IR), and other metabolic dysregulations, potentially influencing graft rejection and long-term survival[9,10].

Given the prevalence and clinical significance of post-transplant obesity, this article aims to provide a systematic introductory review for novice clinicians and basic medical researchers in the field of organ transplantation. By synthesizing multidisciplinary foundational evidence, it seeks to help readers establish a comprehensive conceptual framework for understanding the mechanisms and management strategies of post-transplant obesity (Figure 1, Supplementary Figure 1).

Figure 1 Classification of transplanted organs included in the literature. The pie chart is a classification diagram based on different target organs among the selected literatures, revealing the data volume of different organs related to post-transplant obesity in the current database.

MATERIALS AND METHODS

A systematic search was conducted in PubMed and Web of Science for studies published up from 2020 to 15 July 2025, using the items and free words: ((overweight) OR (obesity)) AND ((post transplantation) OR (post organ transplantation)). Only randomized controlled trials (RCTs), meta-analyses, and systematic reviews were included. Non-empirical literature, such as narrative reviews, commentaries, editorials, conference abstracts, and clinical guidelines, were excluded. Duplicate publications and studies irrelevant to the research topic were also removed. The search strategy focused on identifying relevant terms in titles, abstracts, and keywords. The selection process involved two independent reviewers (Wu LZ and Huang YN) who screened the articles based on predefined inclusion and exclusion criteria. Disagreements were resolved by a third reviewer (Chen KR), who made the final decision in cases of inconsistency. The initial search yielded 1455 articles meeting the inclusion criteria (Figure 2, Tables 1 and 2).

Figure 2  The systematic process of screening research literatures, providing clear literature sources and screening basis for subsequent analyses.

Table 1 Screening results.

Total	Theme-independent	Non-postoperative obesity	Mechanism-free
298	283	6	2
290	109	90	61
290	270	9	11
290	22	176	12
289	247	7	6
1457	931	288	92

Table 2 Classification results.

Total	Liver	Kidney	Heart	Lung
7	/	3	4	/
30	1	7	19	3
0	/	/	/	/
80	6	32	24	13
29	/	13	13	2
146	7	55	60	18

RESULTS

Immunopharmacological factors

Immunosuppressive therapy is indispensable for maintaining allograft survival after solid organ transplantation; however, it also constitutes a primary pathogenic driver of post-transplantation obesity. Among the immunopharmacological agents commonly employed, corticosteroids and calcineurin inhibitors (CNIs)-particularly cyclosporine and tacrolimus-are most frequently implicated in metabolic complications, including excessive weight gain, IR, and dyslipidemia (Table 3)[11-18].

Table 3 Summary of metabolic effects and mechanisms of common.

Immunosuppressant	Major metabolic effects	Proposed mechanisms	Ref.
Glucocorticoids	Hyperphagia, central adiposity, insulin resistance	↑ Appetite via central regulation; ↓ adiponectin, ↑ leptin resistance	[11]
Tacrolimus (CNI)	Impaired glucose tolerance, β-cell apoptosis	Inhibition of PI3K/Akt/mTOR; microbiome alterations	[15]
Cyclosporine (CNI)	Dyslipidemia, insulin resistance	Mitochondrial dysfunction, oxidative stress	[18]
Mycophenolate Mofetil	Dyslipidemia	Synergistic effects when combined with steroids/CNIs	[18]
Azathioprine	Less studied; associated with lipid alterations	Likely indirect or combined effects	[18]

CNI: Calcineurin inhibitor.

Glucocorticoids: Essential immunosuppressants with a heavy metabolic cost. Glucocorticoids remain a cornerstone of induction and maintenance immunosuppression but are well known for their profound metabolic side effects. These agents stimulate hyperphagia by increasing fasting hunger and altering central regulation of appetite. Functional neuroimaging studies reveal that stress-level glucocorticoids reduce cerebral blood flow in regions responsible for appetite control, thereby promoting increased energy intake[11]. Simultaneously, they upregulate lipogenesis, redistribute adipose tissue centrally, and exacerbate IR by interfering with insulin receptor signaling and glucose uptake[12]. Variability in individual glucocorticoid sensitivity has also been linked to differential obesity risk, suggesting a gene-environment-drug interaction in glucocorticoid-induced adiposity[13]. Furthermore, long-term glucocorticoid exposure alters adipokine secretion profiles, notably decreasing adiponectin and increasing leptin resistance, thereby impairing satiety signaling and exacerbating metabolic dysregulation[14].

CNIs: Potent immunosuppressants with diabetogenic consequences. CNIs, particularly tacrolimus, are central to post-transplant immunosuppression but are increasingly recognized for their diabetogenic effects. Tacrolimus impairs pancreatic β-cell function through inhibition of the PI3K/Akt/mTOR signaling pathway, leading to decreased insulin secretion and increased β-cell apoptosis[15]. Beyond its direct pancreatic toxicity, tacrolimus may also induce nephrotoxicity and pancreatic injury, both of which exacerbate glucose dysregulation[16]. Recent research further implicates the gut microbiome as a mediator of CNI-induced metabolic disturbances; alterations in microbial composition and metabolite production have been shown to contribute to impaired glucose tolerance in preclinical models[17]. Collectively, these findings suggest that the diabetogenic risks of CNIs extend beyond traditional mechanisms and may involve complex inter-organ and host-microbiome interactions.

Other immunosuppressants and combined effects: Other immunosuppressive agents, such as azathioprine and mycophenolate mofetil, particularly when used in combination with CNIs and corticosteroids, have been associated with adverse lipid profiles, including elevated triglyceride levels[18]. These combined regimens amplify the risk of metabolic syndrome, especially when administered over prolonged durations.

In aggregate, immunosuppressive drugs exert multifaceted metabolic effects through endocrine, neural, and microbiota-mediated pathways. They disrupt glucose-insulin regulation, stimulate lipid accumulation, and impair energy balance, while also interfering with satiety signaling and adipokine function[19-24]. These mechanisms converge to create a metabolic environment conducive to obesity development, making immunopharmacological modulation both a challenge and a critical therapeutic target in the post-transplantation setting (Table 4).

Table 4 Comparison of post-transplant obesity incidence and influencing factors by organ type.

Index	Adult	Child	Activity	Diet	Ref.
Heart transplant	25-40 per cent of patients’ obesity post-transplantation	The lowest incidence of obesity post-transplantation, the lowest risk of obesity relative to other organ groups	Limited heart function and restricted exercise tolerance	The aggressive use of supplemental nutrition via feeding tubes	[23,24]
Kidney transplantation	21% of patients with CKD have obesity, and CKD patients are the main population for kidney transplantation	The highest incidence of obesity, a cumulative incidence 5-year post-transplantation of 27%	Reduced activity due to dialysis	Supplementary caloric intake via peritoneal dialysis	[22,23]
Liver transplantation	23% of liver transplant candidates have class I obesity, 10% have class II, and 4% have class III	The probability of obesity is lower than that of kidney transplantation and higher than that of heart transplantation	have a critical clinical status at time of transplantation in order to reduce activites	have a critical clinical status at time of transplantation in order to reduce food intake	[23,24]

CKD: Chronic kidney disease.

Postoperative activity level

Transplant surgery is highly invasive, causing significant physiological impact. Traditionally, patients often remain sedentary post-operation, with many facing reduced mobility due to physical or psychological barriers. Concurrently, increased food intake is common for recovery. Studies show higher physical activity reduces daily energy intake and elevates basal metabolic expenditure[19]. Body weight gain is determined by the balance between energy intake and total energy expenditure, which comprises basal metabolic rate (BMR) and activity-induced energy expenditure[20]. Reduced postoperative activity following transplantation lowers energy expenditure, exacerbating positive energy balance and contributing to post-transplant obesity.

Dietary factors

Organ transplantation benefits patients, yet post-transplant weight gain significantly threatens recovery and long-term health. Studies indicate recipients consistently shift towards dietary patterns high in calorie-dense, fatty, and sugary foods.

Core immunosuppressants-glucocorticoids and CNIs-exhibit adipogenic effects. Glucocorticoids stimulate hypothalamic appetite centers, induce IR, promote visceral adiposity, and enhance protein catabolism, ultimately suppressing BMR[21]. Sustained moderate-dose glucocorticoids suppress BMR by 15%-20% (P < 0.01). CNIs dysregulate lipid homeostasis via PPARγ-mediated lipolysis impairment, increasing central adiposity risk (adjusted odds ratio = 2.3; 95%CI: 1.7-3.1)[22]. Prolonged illness fosters a psychological 'compensatory mindset' where patients reward suffering through hedonic eating. Combined with medication-induced taste changes and cultural tonic beliefs, this drives excessive calorie intake. A renal transplant study found one third exceeded caloric recommendations in the first three years post-transplant, developing obesity[23]. Modifying entrenched dietary habits is challenging. Some patients underestimate weight gain's significance, unaware of its strong links to graft dysfunction, cardiovascular risks, and post-transplant diabetes mellitus (PTDM). Complex prescriptions requiring simultaneous management of multiple metabolic parameters (e.g., glycemia, lipids, uric acid, electrolytes) impose substantial burdens. These barriers, compounded by medication-related discomfort and cultural beliefs about nutrition, undermine both motivation and capacity for adherence. Studies indicate compliance with specific restrictions, like rigorous sodium limitation, may fall post-transplantation[24].

Molecular-level factors

Influences on adipokine signaling pathways: Immunosuppressants, particularly CNIs like tacrolimus, disrupt adipokine signaling by altering the secretion and function of key adipokines such as leptin and adiponectin. This interference initiates a cascade of metabolic dysregulation that contributes to IR and PTDM.

Tacrolimus upregulates leptin expression but induces leptin resistance by impairing JAK2/STAT3 signaling in hypothalamic neurons, which normally suppresses appetite and hepatic gluconeogenesis[25,26]. Leptin resistance exacerbates hyperphagia and promotes ectopic lipid deposition in the liver and muscle, further aggravating IR[26].

Tacrolimus reduces adiponectin secretion by 30%–50% in adipose tissue, mediated through inhibition of PPARγ transcriptional activity[25,27]. Low adiponectin diminishes AMPK activation in skeletal muscle and liver, leading to reduced phosphorylation of acetyl-CoA carboxylase (ACC) and impairing fatty acid oxidation. Enhanced hepatic gluconeogenesis via unopposed mTOR/S6K1 signaling[26,27]. Adiponectin's tumor-suppressive and metabolic regulatory roles in glioma cells via AMPK activation further underscore its systemic importance[27].

Immunosuppressants synergize with transplantation-induced inflammation to skew adipokine profiles. Pro-inflammatory cytokines [e.g., tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6] from adipose tissue macrophages suppress adiponectin transcription and amplify leptin resistance[26,28]. Oxidative stress triggered by tacrolimus activates NF-κB in adipocytes, increasing resistin and visfatin secretion. These adipokines directly inhibit insulin receptor substrate 1 (IRS1) tyrosine phosphorylation in skeletal muscle, blunting GLUT4 translocation[25,29] (Table 5).

Table 5 Key adipokine alterations in post-transplantation obesity.

Adipokine	Change	Mechanism	Metabolic Consequence	Ref.
Leptin	↑ Secretion	PPARγ inhibition→Leptin resistance	↑Appetite,↑ hepatic glucose output	[25,26]
Adiponectin	↓Secretion (30%–50%)	Impaired PPARγ/AMPK axis	↓Fatty acid oxidation→lipid accumulation	[25,27]
Resistin	↑ Secretion	NF-κB activation by oxidative stress	IRS1 inhibition →↓glucose uptake	[25,29]

The combined adipokine dysregulation converges on insulin signaling defects. AMPK suppression (from low adiponectin) and mTOR overactivation (from high leptin/resistin) inhibit IRS1/PI3K/Akt signaling, reducing glucose uptake in muscle and adipose tissue[26,27]. Mitochondrial dysfunction in β-cells, driven by tacrolimus-induced oxidative stress, further compromises insulin secretion, creating a vicious cycle of hyperglycemia[25].

Recent studies highlight that gut microbiota alterations under immunosuppressants exacerbate adipokine dysfunction via bile acid signaling, which represses adipose FXR and amplifies inflammation. Targeting adipokine signaling (e.g., with AMPK activators like metformin or adiponectin mimetics) represents a promising strategy to mitigate PTDM[26,27].

Effects on the adipogenesis pathway: After organ transplantation, the incidence of obesity is significantly increased in patients, a phenomenon that is deeply influenced at the molecular level by the transplant-induced inflammatory cascade and oxidative stress, both of which activate the adipogenic pathway through a complex mechanism that promotes an abnormal accumulation of lipids in adipose tissue[30-39]. After transplantation, the activation of the immune system and the allogeneic reaction of the transplanted organ often triggers systemic inflammation, and the inflammatory cascade network characterized by the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β) is formed, which can directly or indirectly activate adipogenic pathways through multiple pathways. On the one hand, inflammatory signals can activate signaling pathways such as NF-κB and JAK/STAT, and upregulate the expression of key adipogenic transcription factors (e.g., PPARγ and C/EBPα). For example, TNF-α can inhibit the negative regulator of PPARγ, SIRT1, or directly promote its phosphorylation, which enhances the transcriptional activity of PPARγ, and drives the differentiation of preadipocytes to mature adipocytes[40,41]. Meanwhile, the inflammatory environment can also alter the expression of adipogenesis-related genes with the help of epigenetic mechanisms (e.g., DNA methylation, histone acetylation), such as IL-6 activating the DNA methyltransferase DNMT, inhibiting the expression of the adipocyte differentiation suppressor Pref-1, and deregulating the inhibition of adipogenesis[36,42]. In addition, extracellular matrix sclerosis caused by inflammatory response can activate mechanotransduction through integrin signaling pathway to promote the proliferation and differentiation of adipocyte precursors, and the abnormal deposition of ECM components can also regulate adipocyte-matrix interactions and affect the efficiency of adipogenesis[34,35]. On the other hand, oxidative stress induced by post-transplantation ischemia-reperfusion injury, immunosuppressant use and other factors, characterized by overproduction of reactive oxygen species (ROS) and reactive nitrogen species, can also activate the adipogenic pathway, and ROS can activate redox-sensitive transcription factors, such as Nrf2, to up-regulate adipogenesis-related gene expression, even though Nrf2 has traditionally been regarded as a key factor in antioxidant defense[33,38]. Although Nrf2 is traditionally regarded as a key antioxidant defense factor, recent studies have shown that under chronic oxidative stress, Nrf2 can directly promote adipogenic gene transcription by binding to the SREBP-1c promoter. Lipid peroxidation caused by oxidative stress can generate aldehydes, such as 4-hydroxynonenal, which modifies the sulfhydryl groups of key adipogenic proteins (e.g., ACC, FAS), altering their enzyme activity or stability, and promoting lipid synthesis[33,38]. In addition, oxidative stress induces a loss of mitochondrial membrane potential and a decrease in ATP synthesis, leading to a shift in cellular energy metabolism from oxidative phosphorylation to glycolysis, and this metabolic reprogramming provides a substrate for lipid synthesis by increasing acetyl-coenzyme A production while activating the AMPK/mTOR pathway to promote the proliferation and differentiation of adipocyte precursors[32,37]. It is worth noting that the inflammatory cascade response and oxidative stress after transplantation do not exist in isolation, but work together to activate the adipogenic pathway through a complex signaling network, e.g., ROS can promote NF-κB nuclear translocation through activation of the IKK complex, thereby upregulating inflammatory cytokines and adipogenic gene expression, inflammatory cytokines (e.g., TNF-α) can induce mitochondrial ROS production, and ROS, in turn, can further amplify the inflammatory response by activating NLRP3 inflammatory vesicles, forming a positive feedback loop that continuously activates the adipogenic pathway[33,39] (Table 6).

Table 6 Molecular pathways and key factors in transplant-associated adipogenesis.

Mechanism type	Specific ways	Key molecules/factors	Effect
Inflammatory cascade activates adipogenic pathways	Activation of signaling pathways[40,41]	NF-Kb, JAK/STAT, TNF-α, SIRT1, PPARy, C/EBPα	Inflammatory signaling activates NF-κB, JAK/STAT pathways, TNF-α enhances PPARV activity by inhibiting SIRT1 or promoting its phosphorylation and up-regulation of key adipogenic transcription factors drives preadipocyte differentiation
	Epigenetic regulation[36,42]	IL-6, DNMT, Pref-1	Activation of DNMT by IL-6 and inhibition of Pref-1 release the suppression of adipogenesis and alteration of adipogenesis-related gene expression by epigenetic mechanisms
	Extracellular matrix effects[34,35]	Integrin signaling pathway ECM components	Inflammation leads to extracellular matrix sclerosis, which promotes proliferation and differentiation of adipocyte precursors through activation of mechanotransduction by the integrin signaling pathway; aberrant deposition of ECM components regulates adipocyte-matrix interactions and affects adipogenic efficiency
Oxidative stress activates adipogenic pathways	Transcription factor activation[33,38]	ROS, Nrf2, SREBP-1c	ROS activate redox-sensitive transcription factors such as Nrf2, which binds to the SREBP.1c promoter under chronic oxidative stress to directly promote adipogenic gene transcription
	lipid peroxidation[33,38]	4-Hydroxynonenal, ACC, FAS	Oxidative stress leads to lipid peroxidation to generate aldehyde products, and modification of sulfhydryl groups of key adipogenic proteins, such as ACC. FAS, alters their enzymatic activity or stability and promotes lipid synthesis
	Metabolic reprogramming[32,37]	mitochondrial membrane potential, ATP, Acetyl Coenzyme A, AMPK/mTOR pathway	Oxidative stress induces the loss of mitochondrial membrane potential, ATP synthesis decreases cellular energy metabolism from oxidative phosphorylation to glycolysis, increases the generation of acetyl-coenzyme A, which provides substrates for fat synthesis, and at the same time activates the AMPK/mTOR pathway to promote the proliferation and differentiation of adipocyte precursors
Inflammation and oxidative stress synergize	Signal network synergy[33,39]	ROS, IKK complex, NF-κB, TNF-α, NLRP3inflammatory, vesicle	ROS activate IKK complex, promote NFKB nuclear translocation, and up-regulate inflammatory cytokines and adipogenic gene expression: TNF-α induces mitochondrial ROS production, and ROS activate NLRP3 inflammatory vesicles, forming a positive feedback loop and continuously activating the adipogenic pathway

TNF-α: Tumor necrosis factor-alpha; SIRT1: Sirtuin 1; C/EBPα: CCAAT/enhancer-binding protein alpha; IL-6: Interleukin-6; DNMT: DNA methyltransferase; Pref-1: Preadipocyte factor-1; ECM: Extracellular matrix; ROS: Reactive oxygen species; Nrf2: Nuclear factor erythroid 2–related factor 2; SREBP-1c: Sterol regulatory element-binding protein 1c; ACC: Acetyl-CoA carboxylase; FAS: Fatty acid synthase; AMPK: AMP-activated protein kinase; mTOR: Mechanistic target of rapamycin; IKK: IκB kinase; NLRP3: NLR family pyrin domain containing 3.

DISCUSSION

One critical avenue for intervention lies in the refinement of immunosuppressive protocols. Reducing the cumulative exposure to metabolically toxic agents, particularly glucocorticoids and tacrolimus, may mitigate their obesogenic effects. Strategies under investigation include dose minimization, steroid-sparing regimens[7], and substitution with metabolically neutral or protective agents. For instance, rapamycin has demonstrated potential protective effects against tacrolimus-induced pancreatic injury via inhibition of the Syk/BLNK/NF-κB pathway[16]. Additionally, novel immunosuppressants with more favorable metabolic profiles should be developed to preserve graft tolerance while minimizing systemic side effects.

Microbiota-targeted strategies also represent a promising adjunct. Vancomycin has been shown to alleviate tacrolimus-induced hyperglycemia by eliminating bacterial β-glucuronidase activity, highlighting the potential for microbiome modulation as a therapeutic strategy[43]. Similarly, agents such as Reg3 g, a regenerating islet-derived protein, have shown efficacy in restoring mitochondrial function and improving pancreatic β-cell performance under tacrolimus exposure[44,45].

Integrated lifestyle interventions combining structured exercise and personalized nutrition are pivotal for mitigating post-transplantation obesity. Tailored aerobic/resistance training (e.g., 30-45 minutes/day, 5 days/week) counters sedentariness and immunosuppressant-induced metabolic suppression. In pediatric renal recipients, such regimens improve insulin sensitivity and reduce adiposity[45], while supervised programs in lung transplant patients significantly lower BMI trajectories[46].

Dietary management must address hyperphagia and cultural barriers. Mediterranean-style diets (high in monounsaturated fats/fiber) reduce LDL cholesterol and weight regain in liver recipients[47]; Family-centered education and meal-timing strategies (e.g., daytime high-protein meals) curb nocturnal overeating and improve adherence[45,46].

Pharmacological interventions targeting immunosuppressant-disrupted molecular pathways-particularly adipokine signaling and adipogenic cascades-hold transformative potential for mitigating post-transplantation obesity. Key strategies focus on AMPK activation, a central regulator countering lipid accumulation and IR: Natural compounds like Saikosaponin A/D inhibit adipogenesis in 3T3-L1 adipocytes by phosphorylating AMPK and MAPK, thereby suppressing PPARγ/C/EBPα expression[48], while Hypericin activates AMPK via PKA signaling to ameliorate leptin resistance and hepatic lipid deposition in vivo[49]. These agents concurrently disrupt NF-κB-driven inflammatory loops and directly oppose glucocorticoid/CNIs toxicity-reversing PPARγ inhibition, restoring adiponectin secretion, and blocking ectopic lipid storage.

Based on the screened literature data, studies on liver and lung transplantation remain relatively scarce. Future research should prioritize investigating the mechanisms underlying post-transplant obesity in these specific organ cohorts to enrich the existing evidence base.

CONCLUSION

Current evidence demonstrates the complexity of etiological mechanisms and therapeutic strategies for post-transplantation obesity. Research indicates that the administration of immunosuppressive agents, postoperative lifestyle modifications, and dysregulation of molecular pathways collectively contribute to obesity development. While optimization of immunosuppressive regimens and lifestyle interventions have demonstrated preventive potential, further clinical investigations are warranted to evaluate their efficacy in improving metabolic outcomes and long-term allograft survival in transplant recipients.

ACKNOWLEDGEMENTS

The authors would like to express their profound gratitude to all contributors included in the RCTs for their efforts in identifying and supplying pertinent data related to their respective studies.