Butaphosphan Effects on Glucose Metabolism Involve Insulin Signaling and Depends on Nutritional Plan

Abstract

Butaphosphan is an organic phosphorus compound used in several species for the prevention of rapid catabolic states, however, the mechanism of action remains unclear. This study aimed at determining the effects of butaphosphan on energy metabolism of mice receiving a normal or hypercaloric diet (HCD) and submitted or not to food restriction. Two experiments were conducted: (1) during nine weeks, animals were fed with HCD (n = 28) ad libitum, and at the 10th week, were submitted to food restriction and received butaphosphan (n = 14) or saline injections (n = 14) (twice a day, for seven days) and; (2) during nine weeks, animals were fed with a control diet (n = 14) or HCD (n = 14) ad libitum, and at the 10th week, all animals were submitted to food restriction and received butaphosphan or saline injections (twice a day, for seven days). In food restriction, butaphosphan preserved epididymal white adipose tissue (WAT) mass, increased glucose, NEFA, and the HOMA index. In mice fed HCD and submitted to food restriction, the butaphosphan preserved epididymal WAT mass. Control diet influences on PI3K, GCK, and Irs1 mRNA expression. In conclusion, butaphosphan increased blood glucose and reduced fat mobilization in overweight mice submitted to caloric restriction, and these effects are influenced by diet.

The Role of Diet on Insulin Sensitivity

“…Approved for use in dairy cows during the postpartum period of negative energy balance in order to avoid an excessive mobilization of body fat, butaphosphan exerts a variety of metabolic actions that depend, at least in part, on the type of animal feeding. Overall, this study demonstrated that butaphosphan treatment could preserve adipose tissue mass and increase blood glucose levels in food-restricted animals by promoting an IR state [ 22 ], which is consistent with human and animal evidence for modulatory roles of dietary phosphate and serum phosphorus on insulin signaling [ 23 ].…”

“…Intriguingly, even perception of sucralose taste impaired insulin responses to OGTT, underscoring the potential of artificial sweeteners to cause profound harm to metabolic health [ 20 ]. Finally, Weiller and colleagues detailed the effects of butaphosphan, an organic source of phosphorus commonly used in veterinary medicine, on insulin sensitivity and glucose metabolism in mice on acute food restriction while receiving either a normal- or a high-calorie diet [ 22 ]. Approved for use in dairy cows during the postpartum period of negative energy balance in order to avoid an excessive mobilization of body fat, butaphosphan exerts a variety of metabolic actions that depend, at least in part, on the type of animal feeding.…”

Use of organic phosphorous butafosfan and vitamin B12 combination in transition dairy cows

“…In contrast, significantly increased concentrations of blood phosphorus were reported in dairy cattle by Furll et al (2010); Krdzalic and Curcic (1976), in mice treated with much higher doses of butafosfan (50 mg/kg b.w.) by Weiller et al (2020) and in ewes by Pereira et al (2013a). Non-ketotic cows treated with iBC produced 2.8 kg more milk per day (calculated) resulting in lower blood phosphorus concentrations (Kreipe et al 2011).…”

“…The most recent in vivo biochemical studies conducted on both butafosfan alone or in combination with VB12 (iBC) showed that it interfered with metabolic function and the energy processes in the organism (Hasi et al 2005a;Furll et al 2010;Kreipe et al 2011;Gomes Jose et al 2012;Nuber et al 2016;Antunes et al 2019;Weiller et al 2020;Scharen et al 2021). We identified seven studies about the effect of butafosfan as a single compound in mice (Hasi et al 2004;Hasi et al 2005a;Weiller et al 2020), in poultry (Hasi et al 2005b;Hasi et al 2005c) and in cattle (Nuber et al 2016;Antunes et al 2019).…”

“…Butafosfan improved liver and muscle glycogen concentrations and promoted significantly the synthesis of ATP and ADP, but decreased AMP in mice (Hasi et al 2004). A study investigating the mode of action of butafosfan (Weiller et al 2020) showed https://doi.org/10.17221/56/2021-VETMED that an injection of butafosfan at 10 × recommended dose rate (50 mg/kg b.w., twice a day, 7 days) in mice fed a hypercaloric diet and then food-restricted, preserved epididymal white adipose tissue mass, reduced fat mobilization, increased blood glucose concentration and the homeostatic model assessment index (insulin resistance index). Mice treated with butafosfan had increased expression of mRNA associated with fatty acid metabolism such as ACOX1 (peroxisomal acyl-coenzyme A oxidase 1), CPTa (carnitine palmitoyltransferase 1A), and ACACa (acetyl-CoA carboxylase alpha) and with glucose metabolism such as IRS2 (insulin receptor substrate 2) and GK (glukokinase).…”