bims-stacyt 2025-03-30 papers

bims-stacyt

Biomed News

on Metabolism and the paracrine crosstalk between cancer and the organism

Issue of 2025–03–30
thirteen papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge

Pre-cachectic changes in amino acid homeostasis precede activation of eIF2α signaling in the liver at the onset of C26 cancer-induced cachexia.
The influence of fatty acid metabolism on T cell function in lung cancer.
Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.
MTFR1 phosphorylation-activated adaptive mitochondrial fusion is essential for colon cancer cell survival during glucose deprivation.
The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21.
Plasticity of the mammalian integrated stress response.
Low pH induces amiloride-sensitive expression of leukemia inhibitory factor in endometrial cells.
SLC3A2-Mediated Lysine Uptake by Cancer Cells Restricts T cell Activity in Hepatocellular Carcinoma.
Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.
Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.
The impact of the tumor microenvironment in the dual burden of obesity-cancer link.
Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.
Association of adipokines with insulin resistance and metabolic syndrome including obesity and diabetes.

iScience. 2025 Mar 21. 28(3): 112030

Pre-cachectic changes in amino acid homeostasis precede activation of eIF2α signaling in the liver at the onset of C26 cancer-induced cachexia.

Ghita Chaouki, Laurent Parry, Cyrielle Vituret, Céline Jousse, Martin Leremboure, Céline Bourgne, Laurent Mosoni, Yoann Delorme, Mehdi Djelloul-Mazouz, Julien Hermet, Julien Averous, Alain Bruhat, Lydie Combaret, Daniel Taillandier, Isabelle Papet, Laure B Bindels, Pierre Fafournoux, Anne-Catherine Maurin.

  The sequence of events associated with cancer cachexia induction needs to be further characterized. Using the C26 mouse model, we found that prior to cachexia, cancer progression was associated with increased levels of IL-6 and growth differentiation factor 15 (GDF15), highly induced production of positive acute phase proteins (APPs) and reduced levels of most amino acids in the systemic circulation, while signal transducer and activator of transcription 3 (STAT3) signaling was induced (1) in the growing spleen, alongside activation of ribosomal protein S6 (rpS6) and alpha subunit of eukaryotic translation initiation factor-2 (eIF2α) signalings, and (2) in the liver, alongside increased positive-APP expression, decreased albumin expression, and upregulation of autophagy. At the onset of cachexia, rpS6 and eIF2α signalings were concomitantly activated in the liver, with increased expression of activating transcription factor 4 (ATF4) target genes involved in amino acid synthesis and transport, as well as autophagy. Data show that pre-cachectic (pre-Cx) alterations in protein/aa homeostasis are followed by activation of eIF2α signaling in the liver, an adaptive mechanism likely regulating protein/amino acid metabolism upon progression to cachexia.

Keywords:  Cancer; Cell biology; Molecular biology

DOI:  https://doi.org/10.1016/j.isci.2025.112030
FEBS J. 2025 Mar 25.

The influence of fatty acid metabolism on T cell function in lung cancer.

Jessica Petiti, Ludovica Arpinati, Alessio Menga, Giovanna Carrà.

  The tumor microenvironment (TME) is a complex ecosystem, encompassing a variety of cellular and non-cellular elements surrounding and interacting with cancer cells, overall promoting tumor growth, immune evasion, and therapy resistance. In the context of solid tumors, factors, such as hypoxia, nutritional competition, increased stress responses, glucose demand, and PD-1 signals strongly influence metabolic alterations in the TME, highly contributing to the maintenance of a tumor-supportive and immune-suppressive milieu. Cancer cell-induced metabolic alterations partly result in an increased fatty acid (FA) metabolism within the TME, which strongly favors the recruitment of immune-suppressive M2 macrophages and myeloid-derived suppressor cells, crucial contributors to T-cell exhaustion, tumor exclusion, and decreased effector functions. The drastic pro-tumoral changes induced by the tumor metabolic rewiring result in signaling loops that support tumor progression and metastatic spreading, and negatively impact therapy efficacy. As tumor- and immune metabolism are increasingly gaining attention due to their potential therapeutic implications, we discuss the effects of altered lipid metabolism on tumor progression, immune response, and therapeutic efficacy in the context of lung cancer. In particular, we focus our analysis on the tumor-induced metabolic alterations experienced by T lymphocytes and the possible strategies to overcome immunotherapy resistance by targeting specific metabolic pathways in T cells.

Keywords:  T‐cell function; cancer metabolism; fatty acid metabolism; lung cancer

DOI:  https://doi.org/10.1111/febs.70081
J Immunother Cancer. 2025 Mar 22. pii: e010057. [Epub ahead of print]13(3):

Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.

Richard McKinnon Walsh, Joseph Ambrose, Jarrid L Jack, Austin E Eades, Bailey A Bye, Mariana Tannus Ruckert, Fanuel Messaggio, Appolinaire A Olou, Prabhakar Chalise, Dong Pei, Michael N VanSaun.

   BACKGROUND: CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands are a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and even adipocytes, they are also secreted by immune-evasive cancer cells. CXC-ligand release is known to occur in response to inflammatory stimuli. Adipose tissue is an endocrine organ and a source of inflammatory signaling peptides. Importantly, adipose-derived cytokines and chemokines are implicated as potential drivers of tumor cell immune evasion; cumulatively, these findings suggest that targeting CXC-ligands may be beneficial in the context of obesity.
METHODS: RNA-sequencing of human PDAC cell lines was used to assess influences of adipose conditioned media on the cancer cell transcriptome. The adipose-induced secretome of PDAC cells was validated with ELISA for induction of CXCL5 secretion. Human tissue data from CPTAC was used to correlate IL-1β and TNF expression with both CXCL5 mRNA and protein levels. CRISPR-Cas9 was used to knockout CXCL5 from a murine PDAC KPC cell line to assess orthotopic tumor studies in syngeneic, diet-induced obese mice. Flow cytometry and immunohistochemistry were used to compare the immune profiles between tumors with or without CXCL5. Mice-bearing CXCL5 competent or deficient tumors were monitored for differential tumor size in response to anti-PD-1 immune checkpoint blockade therapy.
RESULTS: Human adipose tissue conditioned media stimulates CXCL5 secretion from PDAC cells via either IL-1β or TNF; neutralization of both is required to significantly block the release of CXCL5 from tumor cells. Ablation of CXCL5 from tumors promoted an enriched immune phenotype with an unanticipatedly increased number of exhausted CD8 T cells. Application of anti-PD-1 treatment to control tumors failed to alter tumor growth, yet treatment of CXCL5-deficient tumors showed response by significantly diminished tumor mass.
CONCLUSIONS: In summary, our findings show that both TNF and IL-1β can stimulate CXCL5 release from PDAC cells in vitro, which correlates with expression in patient data. CXCL5 depletion in vivo alone is sufficient to promote T cell infiltration into tumors, increasing efficacy and requiring checkpoint blockade inhibition to alleviate tumor burden.

Keywords:  Adenocarcinoma; Gastrointestinal Cancer; Immune Checkpoint Inhibitor

DOI:  https://doi.org/10.1136/jitc-2024-010057
Neoplasia. 2025 Mar 22. pii: S1476-5586(25)00038-7. [Epub ahead of print]63 101159

MTFR1 phosphorylation-activated adaptive mitochondrial fusion is essential for colon cancer cell survival during glucose deprivation.

Nan Zhang, Lu Dong, Sifan Liu, Tingting Ning, Shengtao Zhu.

   BACKGROUND: Mitochondrial dynamics are essential for maintaining cellular function under metabolic stress. However, their role in colon cancer's response to glucose deprivation remains poorly understood.
METHODS: The role of the mitochondrial protein MTFR1 in colon cancer proliferation was evaluated using CCK-8 and colony formation assays. Mass spectrometry identified MTFR1-interacting proteins and phosphorylation sites. Mitochondrial morphology was examined with Mitotracker staining, and mitochondrial function was evaluated using MitoSOX, JC-1 staining, and the Seahorse cell mitochondrial stress test.
RESULTS: We observed that MTFR1 is highly expressed in colon cancer cells and interacts with NEK1 under glucose deprivation. This interaction induces phosphorylation of MTFR1 at serine 119, which promotes mitochondrial fusion and supports mitochondrial function. Consequently, enhanced oxidative phosphorylation improves cellular tolerance to glucose deprivation.
CONCLUSIONS: Our findings highlight the importance of MTFR1 in modulating mitochondrial dynamics and its potential impact on colon cancer cell survival under metabolic stress. These results suggest that MTFR1 serine 119 could be a key regulator of colon cancer cell metabolism and a potential therapeutic target for enhancing cancer cell response to metabolic challenges.

Keywords:  Colorectal cancer; Glucose deprivation; MTFR1; Mitochondrial fusion; NEK1

DOI:  https://doi.org/10.1016/j.neo.2025.101159
Sci Adv. 2025 Mar 28. 11(13): eadt3142

The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21.

Suowen Xu, Zhenghong Liu, Tian Tian, Wenqi Zhao, Zhihua Wang, Monan Liu, Mengyun Xu, Fanshun Zhang, Zhidan Zhang, Meijie Chen, Yanjun Yin, Meiming Su, Wenxiang Fang, Wenhao Pan, Shiyong Liu, Min-Dian Li, Peter J Little, Danielle Kamato, Songyang Zhang, Dongdong Wang, Stefan Offermanns, John R Speakman, Jianping Weng.

Obesity is a debilitating global pandemic with a huge cost on health care due to it being a major underlying risk factor for several diseases. Therefore, there is an unmet medical need for pharmacological interventions to curb obesity. Here, we report that halofuginone, a Food and Drug Administration-approved anti-scleroderma and antiprotozoal drug, is a promising anti-obesity agent in preclinical mouse and pig models. Halofuginone suppressed food intake, increased energy expenditure, and resulted in weight loss in diet-induced obese mice while also alleviating insulin resistance and hepatic steatosis. Using molecular and pharmacological tools with transcriptomics, we identified that halofuginone increases fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) levels via activating integrated stress response. Using Gdf15 and Fgf21 knockout mice, we show that both hormones are necessary to elicit anti-obesity changes. Together, our study reports the beneficial metabolic effects of halofuginone and underscores its utility in treating obesity and its associated metabolic complications, which merits clinical assessment.

DOI: https://doi.org/10.1126/sciadv.adt3142
Nature. 2025 Mar 26.

Plasticity of the mammalian integrated stress response.

Chien-Wen Chen, David Papadopoli, Krzysztof J Szkop, Bo-Jhih Guan, Mohammed Alzahrani, Jing Wu, Raul Jobava, Mais M Asraf, Dawid Krokowski, Anastasios Vourekas, William C Merrick, Anton A Komar, Antonis E Koromilas, Myriam Gorospe, Matthew J Payea, Fangfang Wang, Benjamin L L Clayton, Paul J Tesar, Ashleigh Schaffer, Alexander Miron, Ilya Bederman, Eckhard Jankowsky, Christine Vogel, Leoš Shivaya Valášek, Jonathan D Dinman, Youwei Zhang, Boaz Tirosh, Ola Larsson, Ivan Topisirovic, Maria Hatzoglou.

An increased level of phosphorylation of eukaryotic translation initiation factor 2 subunit-α (eIF2α, encoded by EIF2S1; eIF2α-p) coupled with decreased guanine nucleotide exchange activity of eIF2B is a hallmark of the 'canonical' integrated stress response (c-ISR)1. It is unclear whether impaired eIF2B activity in human diseases including leukodystrophies2, which occurs in the absence of eIF2α-p induction, is synonymous with the c-ISR. Here we describe a mechanism triggered by decreased eIF2B activity, distinct from the c-ISR, which we term the split ISR (s-ISR). The s-ISR is characterized by translational and transcriptional programs that are different from those observed in the c-ISR. Opposite to the c-ISR, the s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (for example, PCK2), resulting in metabolic rewiring required to maintain cellular bioenergetics when eIF2B activity is attenuated. Overall, these data demonstrate a plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of eIF2α-p induction activates the eIF4E-ATF4-PCK2 axis to maintain energy homeostasis.

DOI: https://doi.org/10.1038/s41586-025-08794-6
J Reprod Dev. 2025 Mar 21.

Low pH induces amiloride-sensitive expression of leukemia inhibitory factor in endometrial cells.

Miku Otsugu, Ayumi Mine, Kurumi Fujiwara, Ayako Ichimura, Keiji Yamamoto, Ryo Tachihara, Hideaki Tomura.

  An association has been reported between a lower pH in the uterus and an increased rate of implantation. How low pH regulates endometrial function is unclear. This study investigated the effect of low pH on the expression of leukemia inhibitory factor (LIF), which is crucial for implantation, in a human endometrial carcinoma cell line, rat endometrial stromal cells, and porcine endometrial cells. LIF mRNA expression was quantified by real-time PCR and protein expression was assessed using western blot analysis. LIF mRNA and protein expression increased at low pH in human endometrial carcinoma cells. Increased LIF mRNA expression was also detected at low pH in rat endometrial stromal and porcine endometrial cells, suggesting that low intrauterine pH may create favorable conditions for implantation and endometrial receptivity across species. The increase in LIF mRNA expression in the three cell types was attenuated by the addition of amiloride, indicating that low pH promotes the expression of LIF via amiloride-sensitive molecules in the endometrium.

Keywords:  Amiloride; Endometrial cell; Leukemia inhibitory factor (LIF); Low pH; Sodium-proton exchangers (NHEs)

DOI:  https://doi.org/10.1262/jrd.2024-105
Cancer Res. 2025 Mar 24.

SLC3A2-Mediated Lysine Uptake by Cancer Cells Restricts T cell Activity in Hepatocellular Carcinoma.

Yating Chang, Naizhen Wang, Shaopeng Li, Jiaqi Zhang, Yipeng Rao, Zilong Xu, Lu Li, Hongning Wu, Jun Chen, Yanhua Lin, Xiaoxuan Huang, Pingguo Liu, Jun Zhang, Yueting Liao, Chaolong Lin, Chenghao Huang, Ningshao Xia.

Abnormal amino acid metabolism supports cancer cell proliferation, invasion, and immune evasion in hepatocellular carcinoma (HCC). Previous research exploring amino acid metabolism in HCC has primarily focused on how metabolic reprogramming impacts tumor cells. Here, we focused on the role of amino acid metabolism dysregulation in the crosstalk between HCC and T cells. HCC cells disrupted lysine uptake in T cells, leading to impaired T cell immunity. Lysine deprivation decreased STAT3 levels in T cells, inhibiting T cell proliferation and effector function and ultimately promoting tumor progression. Mechanistically, HCC cells outcompeted T cells for lysine by expressing high levels of the lysine transporter SLC3A2. Clinically, elevated SLC3A2 expression correlated with poor survival and was linked to dysregulated T cell functional gene signatures in HCC patients. Furthermore, the multikinase inhibitor lenvatinib induced a c-Myc-SLC3A2 regulatory axis that limited the efficacy of lenvatinib treatment. Lysine supplementation enhanced tumor sensitivity to combined treatment with lenvatinib and anti-PD-1 immunotherapy. These findings suggest that lysine supplementation is a potential therapeutic strategy for treating HCC and enhancing the sensitivity of HCC to tyrosine kinase inhibitors and immune checkpoint blockade.

DOI: https://doi.org/10.1158/0008-5472.CAN-24-3180
Biomed Pharmacother. 2025 Mar 22. pii: S0753-3322(25)00200-8. [Epub ahead of print]186 118006

Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.

Gioia Heravi, Zhenjie Liu, Mackenzie Herroon, Alexis Wilson, Yang-Yi Fan, Yang Jiang, Nivisa Vakeesan, Li Tao, Zheyun Peng, Kezhong Zhang, Jing Li, Robert S Chapkin, Izabela Podgorski, Wanqing Liu.

   OBJECTIVE: Fatty Acid Desaturase 1 (FADS1) is a rate-limiting enzyme controlling the bioproduction of long-chain polyunsaturated fatty acids (PUFAs). Increasing studies suggest that FADS1 is a potential cancer target. Our previous research has demonstrated the significant role of FADS1 in cancer biology and patient survival, especially in kidney cancers. We aim to explore the underlying mechanism in this study.
METHOD AND RESULTS: We found that pharmacological inhibition or knockdown of the expression of FADS1 significantly reduced the intracellular conversion of long-chain PUFAs, effectively inhibits renal cancer cell proliferation, and induces cell cycle arrest. The stable knockdown of FADS1 also significantly inhibits tumor formation in vivo. Mechanistically, we showed that while FADS1 inhibition induces endoplasmic reticulum (ER) stress, FADS1 expression is augmented by ER-stress inducer, suggesting a necessary role of PUFA production in response to ER stress. FADS1-inhibition sensitized cellular response to ER stress inducers, leading to cell apoptosis. Also, FADS1 inhibition-induced ER stress leads to activation of the PERK/eIF2α/ATF4/ATF3 pathway. Inhibiting PERK or knockdown of ATF3 rescued FADS1 inhibition-induced ER stress and cell growth suppression, while ATF3-overexpression aggravates the FADS1 inhibition-induced cell growth suppression and leads to cell death. Metabolomic analysis revealed that FADS1 inhibition results in decreased level of UPD-N-Acetylglucosamine, a critical mediator of the unfolded protein response, as well as impaired biosynthesis of nucleotides, possibly accounting for the cell cycle arrest.
CONCLUSION: Our findings suggest that PUFA desaturation is crucial for rescuing cancer cells from persistent ER stress, supporting FADS1 as a new therapeutic target.

Keywords:  ATF3; ER stress; FADS1; Kidney cancer; PUFA

DOI:  https://doi.org/10.1016/j.biopha.2025.118006
Cell Rep Med. 2025 Mar 22. pii: S2666-3791(25)00115-6. [Epub ahead of print] 102042

Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.

Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard.

  Interleukin-6 (IL-6) knockout mice and humans treated with IL-6 receptor blockade gain adipose tissue mass. This study investigates whether basal IL-6 activity (resting IL-6 levels) influences fat storage during fasting and postprandial states. Using stable-isotope tracer techniques and IL-6 receptor blockade with tocilizumab, we examine fat kinetics in humans. Blocking basal IL-6 activity reduces fasting whole-body lipolysis, decreases hormone-sensitive lipase (HSL) phosphorylation and fatty acid release in adipose tissue, and impairs postprandial fatty acid uptake in the leg. These results suggest diminished fatty acid uptake and oxidation in skeletal muscle, along with enhanced fatty acid entrapment in adipose tissue, which may account for the increased adiposity in the absence of IL-6 activity. Additionally, IL-6 blockade increases the escape of meal-derived fatty acids into the bloodstream. Whether this affects fatty acid storage and lipotoxicity in other tissues warrants further investigation. This study was registered at ClinicalTrials.gov (NCT04687540).

Keywords:  fasting; fatty acids; homeostasis; humans; interleukin-6; isotopes; lipolysis; nutrients; obesity; tocilizumab

DOI:  https://doi.org/10.1016/j.xcrm.2025.102042
Semin Cancer Biol. 2025 Mar 22. pii: S1044-579X(25)00048-3. [Epub ahead of print]112 36-42

The impact of the tumor microenvironment in the dual burden of obesity-cancer link.

Serena Sagliocchi, Lucia Acampora, Biagio Barone, Felice Crocetto, Monica Dentice.

  Obesity induces systemic perturbations of tissue homeostasis, leading to dyslipidemia, insulin resistance and chronic state of inflammation. Evidence from clinical and preclinical studies links excess of adiposity with increased cancer incidence and suggests that chronic inflammation may contribute to increased cancer risk in obese patients. Over the last decades of obesity research, multifaced and complicated effects of abnormal or excessive expansion of Adipose Tissue have been uncovered. In particular, it is widely described how obesity can exacerbate the tumorigenesis for instance by fueling soluble signals and adipokines and by enhancing tissue inflammation and altering the hormonal balance. Less is known about the paracrine effects of the cancer-associated adipocytes on the tumor cells and still poorly explored is the reciprocal communication between cancer cells and the adipose component of the tumor microenvironment (TME). In this review, we will address the mechanisms by which the peritumoral Adipose Tissue can influence the dynamics of tumoral cells. We will discuss how obesity-induced changes in the tumor microenvironment may enhance tumor growth and aggressive characteristics leading to increased invasiveness and metastatic progression of cancer that leads to a worsen cancer survival in obese subjects. We conclude that targeting the peritumoral adipose component of the TME would be a therapeutic option to prevent cancer development.

Keywords:  Cancer Associated Adipocytes; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.semcancer.2025.03.001
Proc Natl Acad Sci U S A. 2025 Apr;122(13): e2424046122

Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.

Claire A Chaikin, Abhishek V Thakkar, Adam W T Steffeck, Eric M Pfrender, Kaitlyn Hung, Pei Zhu, Nathan J Waldeck, Rino Nozawa, Weimin Song, Christopher R Futtner, Mattia Quattrocelli, Joseph Bass, Issam Ben-Sahra, Clara B Peek.

  Disruptions of circadian rhythms are widespread in modern society and lead to accelerated and worsened symptoms of metabolic syndrome. In healthy mice, the circadian clock factor BMAL1 is required for skeletal muscle function and metabolism. However, the importance of muscle BMAL1 in the development of metabolic diseases, such as diet-induced obesity (DIO), remains unclear. Here, we demonstrate that skeletal muscle-specific BMAL1-deficient mice exhibit worsened glucose tolerance upon high-fat diet feeding, despite no evidence of increased weight gain. Metabolite profiling from Bmal1-deficient muscles revealed impaired glucose utilization specifically at early steps in glycolysis that dictate the switch between anabolic and catabolic glucose fate. We provide evidence that this is due to abnormal control of the nutrient stress-responsive hypoxia-inducible factor (HIF) pathway. Genetic HIF1α stabilization in muscle Bmal1-deficient mice restores glucose tolerance and expression of 217/736 dysregulated genes during DIO, including glycolytic enzymes. Together, these data indicate that during DIO, skeletal muscle BMAL1 is an important regulator of HIF-driven glycolysis and metabolic flexibility, which influences the development of high-fat-diet-induced glucose intolerance.

Keywords:  circadian rhythm; diet-induced obesity; hypoxia; skeletal muscle

DOI:  https://doi.org/10.1073/pnas.2424046122
GHM Open. 2023 Aug 31. 3(1): 7-19

Association of adipokines with insulin resistance and metabolic syndrome including obesity and diabetes.

Abhishek Gupta, Priyanka Gupta, Arun Kumar Singh, Vani Gupta.

  Adipose tissue (AT) acts as a highly active endocrine organ, which secretes a wide range of adipokine hormones. In the past few years, several adipokines (leptin, adiponectin, resistin etc.) have been discovered showing metabolic consequences in relation to insulin resistance (IR), obesity and diabetes. These adipokines are considered to be an important component playing an important role in the regulation of energy metabolism. They have been shown to be involved in the pathogenesis of metabolic syndrome (MetS) and cardiac diseases. The current article provides a holistic summary of recent knowledge on adipokines and emphasizes their importance in association with IR, obesity, diabetes and MetS. Adipokines such as leptin, adiponectin, resistin and tumor necrosis factor-alpha (TNF-α) have been involved in the regulation of an array of metabolic functions and disease associated with it, e.g. appetite and energy balance of the body, suppression of atherosclerosis and liver fibrosis, obesity with type 2 diabetes (T2D) and IR. An important adipokine, Interleukin-6 (IL-6), also correlates positively with human obesity and IR and also the elevated level of IL-6 predicts development of T2D. All of these hormones have important correlation with energy homeostasis, glucose and lipid metabolism, cardiovascular function and immunity. All the possible connections have extended the biological emphasis of AT secreted adipokines as an investigator in the development of MetS, and are now no longer considered as only an energy storage site.

Keywords:  adipose tissue; appetite; glucose; homeostasis; lipid

DOI:  https://doi.org/10.35772/ghmo.2023.01004