bims-stacyt 2024-01-28 papers

Molecules. 2024 Jan 21. pii: 531. [Epub ahead of print]29(2):

CD36: The Bridge between Lipids and Tumors.

Xuan Zhou, Manman Su, Jungu Lu, Deming Li, Xinhui Niu, Yi Wang.

It has been found that the development of some cancers can be attributed to obesity, which is associated with the excessive intake of lipids. Cancer cells undergo metabolic reprogramming, shifting from utilizing glucose to fatty acids (FAs) for energy. CD36, a lipid transporter, is highly expressed in certain kinds of cancer cells. High expressions of CD36 in tumor cells triggers FA uptake and lipid accumulation, promoting rapid tumor growth and initiating metastasis. Meanwhile, immune cells in the tumor microenvironment overexpress CD36 and undergo metabolic reprogramming. CD36-mediated FA uptake leads to lipid accumulation and has immunosuppressive effects. This paper reviews the types of FAs associated with cancer, high expressions of CD36 that promote cancer development and progression, effects of CD36 on different immune cells in the tumor microenvironment, and the current status of CD36 as a therapeutic target for the treatment of tumors with high CD36 expression.

Keywords: CD36; fatty acid; immunosuppress; lipid; metastasis-initiating cells

DOI: https://doi.org/10.3390/molecules29020531

Biomedicines. 2024 Jan 03. pii: 97. [Epub ahead of print]12(1):

The Role of Adipokines in Tumor Progression and Its Association with Obesity.

Jae Won Kim, Jun Hyeok Kim, Yoon Jae Lee.

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis.

Keywords: adipokine; obesity; tumorigenesis

DOI: https://doi.org/10.3390/biomedicines12010097

Nat Commun. 2024 Jan 20. 15(1): 627

Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice.

Xue Yang, Jianming Wang, Chun-Yuan Chang, Fan Zhou, Juan Liu, Huiting Xu, Maria Ibrahim, Maria Gomez, Grace L Guo, Hao Liu, Wei-Xing Zong, Fredric E Wondisford, Xiaoyang Su, Eileen White, Zhaohui Feng, Wenwei Hu.

Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia.

DOI: https://doi.org/10.1038/s41467-024-44924-w

Cancer Drug Resist. 2023 ;6(4): 748-767

Unlocking antitumor immunity with adenosine receptor blockers.

Victoria A Remley, Joel Linden, Todd W Bauer, Julien Dimastromatteo.

Tumors survive by creating a tumor microenvironment (TME) that suppresses antitumor immunity. The TME suppresses the immune system by limiting antigen presentation, inhibiting lymphocyte and natural killer (NK) cell activation, and facilitating T cell exhaustion. Checkpoint inhibitors like anti-PD-1 and anti-CTLA4 are immunostimulatory antibodies, and their blockade extends the survival of some but not all cancer patients. Extracellular adenosine triphosphate (ATP) is abundant in inflamed tumors, and its metabolite, adenosine (ADO), is a driver of immunosuppression mediated by adenosine A2A receptors (A2AR) and adenosine A2B receptors (A2BR) found on tumor-associated lymphoid and myeloid cells. This review will focus on adenosine as a key checkpoint inhibitor-like immunosuppressive player in the TME and how reducing adenosine production or blocking A2AR and A2BR enhances antitumor immunity.

Keywords: Immunotherapy; adenosine; adenosine A2A receptors (A2AR); adenosine A2B receptors (A2BR); adenosine receptors; immune cells; tumor cells; tumor microenvironment

DOI: https://doi.org/10.20517/cdr.2023.63

Obesity (Silver Spring). 2024 Jan 22.

Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume.

Andrea Mendez-Gutierrez, Concepcion M Aguilera, Rubén Cereijo, Francisco J Osuna-Prieto, Borja Martinez-Tellez, Maria C Rico, David Sanchez-Infantes, Francesc Villarroya, Jonatan R Ruiz, Guillermo Sanchez-Delgado.

OBJECTIVE: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans.
METHODS: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 ± 2.3 y; 24.9 ± 5.1 kg/m2 ). BAT volume, 18 F-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure.
RESULTS: Cold exposure increased the concentration of CXCL14 (Δ2h = 0.58 ± 0.98 ng/mL; p = 0.007), GDF15 (Δ2h = 19.63 ± 46.2 pg/mL; p = 0.013), FGF21 (Δ2h = 33.72 ± 55.13 pg/mL; p = 0.003), and IL6 (Δ1h = 1.98 ± 3.56 pg/mL; p = 0.048) and reduced BMP8b (Δ2h = -37.12 ± 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Δ2h: β = 0.456; R2 = 0.307; p = 0.001), but not with 18 F-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity.
CONCLUSIONS: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.

DOI: https://doi.org/10.1002/oby.23970