Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression

Nguyen, Hai P.; Sheng, Rory; Murray, Elizabeth; Ito, Yusuke; Bruck, Michael; Biellak, Cassidy; An, Kelly; Lynce, Filipa; Magbanua, Mark Jesus M.; Huppert, Laura A; Hammerlindl, Heinz; Esserman, Laura J.; Rosenbluth, Jennifer M.; Ahituv, Nadav

doi:10.1101/2023.03.28.534564

Cited by 2 publications

(3 citation statements)

References 90 publications

(104 reference statements)

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“…Multi-objective optimality (Hart et al, 2015) Cancer Multicellular nutrient constraints and GEMs (J. Cancer Multicellular bioenergy constraints (Liu et al, 2013;Zhang et al, 2019) Cancer Multicellular resource competition (Brand et al, 2016;Chang et al, 2015;Nguyen et al, 2023;Reinfeld et al, 2021;Seki et al, 2022) Diabetes Nutrient and machinery constraints (Zisman et al, 2000) Obesity Nutrient imbalances (Dai et al, 2022;Simpson and Raubenheimer, 2005) 4. Appendix…”

Section: Discussionmentioning

confidence: 99%

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Resource Allocation in Mammalian Systems

Baghdassarian,

Lewis

2023

Preprint

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Cells execute biological functions to support phenotypes such as growth, migration, and secretion. Complementarily, each function of a cell has resource costs that constrain phenotype. Resource allocation by a cell allows it to manage these costs and optimize their phenotypes. In fact, the management of resource constraints (e.g., nutrient availability, bioenergetic capacity, and macromolecular machinery production) shape activity and ultimately impact phenotype. In mammalian systems, quantification of resource allocation provides important insights into higher-order multicellular functions; it shapes intercellular interactions and relays environmental cues for tissues to coordinate individual cells to overcome resource constraints and achieve population-level behavior. Furthermore, these constraints, objectives, and phenotypes are context-dependent, with cells adapting their behavior according to their microenvironment, resulting in distinct steady-states. This review will highlight the biological insights gained from probing resource allocation in mammalian cells and tissues.

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Section: Discussionmentioning

confidence: 99%

“…However, the presence of other nutrient sources and cell types may mitigate the role of competition (Reinfeld et al, 2021). Recent work has leveraged the high resource demands of cancer cells by engineering adipocyte glucose and lipid metabolism to outcompete tumors (Nguyen et al, 2023;Seki et al, 2022).…”

Section: Resource Competition Maintains Homeostasismentioning

confidence: 99%

Resource Allocation in Mammalian Systems

Baghdassarian,

Lewis

2023

Preprint

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“…Brown adipose tissue (BAT) and beige adipose tissue, known as one type of adaptive thermogenic adipose tissue, dissipate energy in the form of heat and offer the therapeutic potential to counteract obesity and metabolic disorders [6]. BAT produces heat through non-oxidative uncoupling, which dissipates energy via non-shivering thermogenesis, increasing adipocyte glucose uptake and lipid metabolism [7]. In addition to its thermogenic functions, BAT can also regulate energy metabolism in mice [8].…”

Section: Introductionmentioning

confidence: 99%

The Lipid-Metabolism-Associated Anti-Obesity Properties of Rapeseed Diacylglycerol Oil

Mao,

Zheng,

et al. 2024

Nutrients

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To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine.

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Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression

Cited by 2 publications

References 90 publications

Resource Allocation in Mammalian Systems

Resource Allocation in Mammalian Systems

The Lipid-Metabolism-Associated Anti-Obesity Properties of Rapeseed Diacylglycerol Oil

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