Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker-256 tumor-bearing rats Hely de Morais, Suéllen Kathiane Fernandes Vilas Bôas, Camila O. de Souza, Daniele Romani Miksza, Carolina C. L. Moreira, et al. Cell Biochemistry and Function, 2023 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.
Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2 Alef Aragão Carneiro dos Santos, Luiz Eduardo Rodrigues, Amanda Lins Alecrim-Zeza, Liliane de Araújo Ferreira, Caio dos Santos Trettel, et al. Frontiers in Microbiology, 2022 Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.
Infusion of high concentration of lactate in perfused liver, simulating in vivo hyperlactatemia, prevents the reduction of gluconeogenesis in Walker-256 tumor-bearing rats Isabele Gonçalves Frasson‐Uemura, Giuliana Regina Biazi, Daniele Romani Miksza, Carolina Campos Lima Moreira, Priscila Cassolla, et al. Journal of Cellular Biochemistry, 2019 Gluconeogenesis (GN) is increased in patients with cancer cachexia, but is reduced in liver perfusion of Walker‐256 tumor‐bearing cachectic rats (TB rats). The causes of these differences are unknown. We investigated the influence of circulating concentrations of lactate (NADH generator) and NADH on GN in perfused livers of TB rats. Lactate, at concentrations similar to those found on days 5 (3.0 mM), 8 (5.5 mM), and 12 (8.0 mM) of the tumor, prevented the reduction of GN from 2.0 mM lactate (lactatemia of healthy rat) in TB rats. NADH, 50 or 75 μM, but not 25 μM, increased GN from 2.0 mM lactate in TB rats to higher values than healthy rats. High concentrations of pyruvate (no NADH generator, 5.0 and 8.0 mM) did not prevent the reduction of GN from 2.0 mM pyruvate in TB rats. However, 50 or 75 μM NADH, but not 25 μM, increased GN from 2.0 mM pyruvate in TB rats to similar or higher values than healthy rats. High concentration of glutamine (NADH generator, 2.5 mM) or 50 μM NADH prevented the reduction of GN from 1 mM glutamine in TB rats. Intraperitoneal administration of pyruvate (1.0 mg/kg) or glutamine (0.5 mg/kg) similarly increased the glycemia of healthy and TB rats. In conclusion, high lactate concentration, similar to hyperlactatemia, prevented the reduction of GN in perfused livers of TB rats, an effect probably caused by the increased redox potential (NADH/NAD+). Thus, the decreased GN in livers from TB rats is due, at least in part, to the absence of simulation of in vivo hyperlactatemia in liver perfusion studies.
