Intravenous Infusions of Glycerol Versus Propylene Glycol for the Regulation of Negative Energy Balance in Sheep: A Randomized Trial

Abstract

Simple SummaryPropylene glycol (PG) and glycerol are common energy substances used to supplement the feed of transitioning ruminants in order to minimize the development of metabolic disorders related to energy deficiency. Their effects on the energetic status of the animal have been, thus far, studied mostly by oral administration, which exposes them to substantial microbial metabolism in the rumen. This study compared the direct metabolic effects of these substances following their intravenous (IV) infusion. We found that glycerol was highly glucogenic and insulinotropic, as expected. However, surprisingly, PG had no significant effect on the circulating levels of glucose or insulin. Unlike glycerol, PG significantly raised circulating lactate levels and showed some potential tissue damage activity. Our study points to glycerol, rather than PG, as a potential IV treatment for efficient relief of hypoglycemia and hyperketonemia.AbstractNegative energy balance (NEB) is a state of insufficient dietary-energy consumption, characterized by the breakdown of adipose fat to meet the physiological energy expenditure. Extensive NEB, as common in high-yielding transitioning ruminants, drives significant metabolic disturbance and pathologies such as pregnancy toxemia and ketosis. Strategies to minimize the severity of NEB include the use of energy-dense feed supplements, like glycerol and propylene glycol (PG), or IV glucose infusion during severe hypoglycemia. PG and glycerol have been studied mainly by oral or ruminal administration, which exposes them to substantial metabolism in the digestive system. To investigate their direct benefits to mitigating NEB, we intravenously infused them into sheep induced into NEB by feed restriction. Sixteen 5-month-old ewe lambs at NEB were IV-treated with 170 mL isotonic saline containing 15% glycerol or 15% PG. Both PG and glycerol effectively reduced hyperketonemia by 57% and 61%, and inhibited adipose lipolysis by 73.6% and 73.3%, respectively. Surprisingly, only glycerol was glucogenic (p < 0.0001) and insulinotropic (p < 0.0075), while PG was primarily utilized for production of lactate (p < 0.0001). Tissue-damage biomarkers indicated hemolytic activity for PG. This study revealed glycerol as a superior IV treatment for effective relief of NEB. Since it carries no risk of glucose overloading, glycerol IV infusion may also have clinical advantages over glucose for treatment of pregnancy toxemia and ketosis.

Hyperglycemia-stimulating diet induces liver steatosis in sheep

“…In previous studies with sheep 16 , we found that feeding growing lambs a carbohydrates-rich grain-concentrate ration induces substantial hyperglycemia, with ~ 40% higher blood glucose levels than in lambs raised on a hay-based ration. Based on this observation and on the fact that sheep, as humans, are willing to overeat, we hypothesized that feeding them with that hyperglycemia-stimulating diet for an extended period will induce hepatic steatosis.…”

Efficacy of Different Drenching Regimens of Gluconeogenic Precursors during Transition Period on Body Condition Score, Production, Reproductive Performance, Subclinical Ketosis and Economics of Dairy Cows

“…Additionally, Piantoni and Allen [9] concluded that dosing 300 mL of PG to the cranial reticulo-rumen is more effective for ketosis treatment than dosing the double quantity of G due to the extensive metabolism of G by ruminal microbes to metabolites that are not glucogenic and added that adding G to the recommended dose of PG is doubtful to provide additional benefit. Intravenous administration of glycerol and PG effectively reduced hyperketonemia and lipolysis [32].…”

“…As a result, PG and G have different pathways to be metabolized into glucose. Therefore, their mixture in GPG250 is beneficial for hepatic synthesis of glucose [32,40].…”

“…In the liver, PG is metabolized into lactate and subsequently to glucose [ 30 ] which can support the fetal unit of placenta during gestation [ 4 ]. Constantly, the lactate response to G was minor compared to its major response to PG and then the faster drop in BHB level was observed in response to PG as compared to G. However, the more powerful stimulation of insulin release was observed in G when compared by PG and contributed significantly to the reduction of BHB level [ 32 ]. Glycerol can alleviate the hyperketonemia by substantial hyperglycemia and consequently, increases the capacity of oxidation of acetyl-CoA via the tricarboxylic acid (TCA) TCA cycle which depletes precursors for ketone bodies synthesis [ 17 ].…”

Validation of a handheld β-hydroxybutyrate acid meter to identify hyperketonaemia in ewes

“…This mobilization increases initially non-esterified fatty acids in the liver that by its turn is partially transformed in ketone bodies, mainly β-hydroxybutyrate acid (BHB), but also acetoacetate and acetone (Radostits et al, 2007). The BHB may also become elevated in the bloodstream due to mobilization of the body's reserves, especially when there is a negative energy balance in lean pregnant ewes (Radostits et al, 2007;Kalyesubula et al, 2019). Blood ketosis can also evolve to a nervous condition (nervous ketosis) caused by a BHB-derived product, the isopropanol (Araújo et al, 2014).…”