Table 1.
Potential therapeutic strategies for lipopenia in CAC.
| Therapy strategy | Object | Evidence | Reference |
|---|---|---|---|
| Exercise training | Patients with cancer | Aerobic and resistance exercise can improve patients’ muscle strength and decrease the levels of TNF-α and CRP. | (148, 149) |
| NSAIDs | Patients with CAC | A pilot study shows patients who received celecoxib experienced statistically significant increases in weight and BMI over controls, NSAIDs may improve weight in CAC patients. | (150, 151) |
| Unsaturated fatty acid | Patients with digestive system neoplasm | The plasma levels of unsaturated fatty acids were decreased in patients with cachexia. Supplementation with omega-3 fatty acids significantly increased skeletal muscle mass and decreased IL-6 and TNF-α in patients. | (152–154) |
| Enteral feeding | Patients with CAC | Enteral feeding is associated with improvement in decreasing body fat mass and inflammatory markers (CRP) and increasing in lean body mass. | (155) |
| Ghrelin | Cancer patients with anorexia | Ghrelin increases the energy intake of cancer patients with anorexia. It’s found to have a predominantly positive effect on growth hormone plasma levels, weight gain, increases in lean mass, and reductions in loss of adipose tissue. |
(156, 157) |
| Megestrol | Patients with CAC | High dose megestrol can significantly improve the appetite and body weight of some cancer patients with cachexia, especially the body fat mass. | (158) |
| Gut microbiome | Patients with CAC | There are differences in gut microbiota between CAC patients and non-cachexic people, however, in one prospective study, fecal microbiota transplantation is reported to be negative. | (130, 155) |
| Anti-diabetic agents | In vitro model and murine model | Metformin can deactivate HSL and counteract TNF-α induced lipolysis thereby increasing lipid synthesis and decreasing WAT browning. Rosiglitazone is able to rescue breast cell induced lipid accumulation. |
(159, 160) |
| Lipid lowering agents | Rat model of CAC | Simvastatin attenuates loss of body weight as well as muscle mass and improves cardiac function. | (161) |
| AMPK-stabilizing peptide (ACIP) | In vitro model and tumor-bearing murine model | ACIP is able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on AMPK. | (116) |
| Carnosol | In vitro model and tumor-bearing murine model | Carnosol and its analogues exhibits anti-cachexia effects mainly by inhibiting TNF-α/NF-κB pathway and decreasing muscle and adipose tissue loss. | (162) |
| Piceatannol | In vitro model and tumor-bearing murine model | Piceatannol can modulate the stability of lipolytic proteins, protect tumor-bearing mice against weight-loss in early stage in CAC through preserving adipose tissue. | (20) |
| Farrerol | In vitro model | Farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. | (163) |
| ESM | Murine model | ESM supplementation ameliorates anorexia, lean fat tissue mass, skeletal muscle wasting, reduced physical function, lipid metabolism and microbial dysbiosis. | (129) |
| Anti-PTHrP antibody | In vitro model and tumor-bearing murine model | Neutralization of PTHrP in tumor-bearing mice blocks adipose tissue browning and also loss of muscle mass and strength. It also prevents the lipolytic effects of extracellular vesicles. | (56, 104) |
| Anti-IL-6 receptor antibody | Murine model | Anti-IL-6 receptor antibody can inhibit WAT lipolysis and browning in cachectic mice. | (80) |
| Selective β3-AR antagonist | Tumor-bearing murine model | Treating mice with the selective β3-AR antagonist ameliorates cachexia and decreases UCP1 levels in subcutaneous WAT. | (55) |
| Anti-GDF15-GFRAL antibody (3P10) | Tumor-bearing murine model | 3P10 targets GFRAL and inhibits RET signaling by preventing the GDF15-driven interaction of RET with GFRAL on the cell surface. Treatment with 3P10 reverses excessive lipid oxidation in tumor-bearing mice and prevents CAC, even under calorie-restricted conditions. | (120) |
TNF-α, tumor necrosis factor-α; NSAIDs, non-steroidal anti-inflammatory drugs; CAC, cancer-associated cachexia; IL-6, interleukin-6; CRP, C-reactive-protein; HSL, hormone-sensitive lipase; WAT, white adipose tissue; AMPK, adenosine 5’-monophosphate (AMP)-dependent protein kinase; NF-κB, nuclear factor kappa-B; ESM, eggshell membrane; PTHrP, parathyroid hormone related protein; β3-AR, adrenoceptor beta 3; UCP1, uncoupling protein 1; GDF15, growth differentiation factor 15; GFRAL, GDNF family receptor alpha like; RET, ret proto-oncogene.