Abnormal lipid metabolism in cancer-associated cachexia and potential therapy strategy

Fang, Ruoxin; Liu, Yan; Liao, Zhengkai

doi:10.3389/fonc.2023.1123567

Cited by 7 publications

(2 citation statements)

References 170 publications

(220 reference statements)

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“…Similarly to our findings, other authors described that the mechanisms of increased lipolysis in cancer cachexia were mainly determined by enhanced expression and function of adipocyte HSL [ 28 ]. In this regard, adipose tissue gene expression may be modulated by both cancer and immune cells (such as macrophages and lymphocytes) through the release of cytokines or hormones, such as IL-6, TNF-α, zinc-α 2-glycoprotein, and catecholamines, which can promote lipolysis and reduce insulin sensitivity in cancer patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

Tambaro,

Imbimbo,

Ferraro

et al. 2024

Cancer Metab

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Background Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia. Methods We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5. Results We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027). Conclusion In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.

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Section: Discussionmentioning

confidence: 99%

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

Tambaro,

Imbimbo,

Ferraro

et al. 2024

Cancer Metab

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“…It is characterized by progressive body weight loss, caused by depletion of fat and muscle mass, resulting from the predominance of catabolism and the reduction of anabolism. [1][2][3][4][5][6][7] It is a limiting factor for the effectiveness of oncological treatments (chemotherapy, radiotherapy, and surgery) and is associated with decreased quality of life and increased mortality. [8][9][10] Although catabolic factors produced by tumor cells, such as proteolysis-inducing factor (PIF) and lipid-mobilizing factor (LMF), and by the host's immune system, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) and IL-6, have been recognized as the main mediators of cachexia, 1,3,[11][12][13][14][15][16] the INS resistance may also play an important role in the development of cancer cachexia, as INS has potent anabolic and anticatabolic effects on lipid and protein metabolism.…”

Section: Introductionmentioning

confidence: 99%

Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker‐256 tumor‐bearing rats

de Morais,

Bôas,

de Souza

et al. 2023

Cell Biochemistry & Function

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Insulin (INS) resistance is often found in cancer‐bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker‐256 tumor‐bearing rats (TB rats). INS hepatic sensitivity and INS resistance‐inducing factors, such as free fatty acids (FFA) and tumor necrosis factor‐α (TNF‐α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = −.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF‐α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.

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Combination therapy of corylifol A and anamorelin attenuates cachexia by decreasing pro-inflammatory cytokines, inhibiting lipolysis and increasing food intake in a murine colon cancer model

Li,

Zhang,

Deng

et al. 2024

Discov Med

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Abnormal lipid metabolism in cancer-associated cachexia and potential therapy strategy

Cited by 7 publications

References 170 publications

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker‐256 tumor‐bearing rats

Combination therapy of corylifol A and anamorelin attenuates cachexia by decreasing pro-inflammatory cytokines, inhibiting lipolysis and increasing food intake in a murine colon cancer model

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