Treatment of lactating sows with clofibrate as a synthetic agonist of PPARα does not influence milk fat content and gains of litters

Abstract

BackgroundIn rats, it has been observed that treatment with activators of peroxisome proliferator-activated receptor α (PPARα) disturbs metabolic adaptations during lactation, which in turn lead to a reduction of milk fat content and gains of litters during the suckling period. It has not yet been investigated whether agonists of PPARα are impairing milk production of lactating sows in a similar manner as in rats. Therefore, the present study aimed to investigate the effect of treatment with clofibrate, a strong synthetic agonist of PPARα, on milk composition and litter gains in lactating sows.ResultsTwenty lactating sows received either a basal diet (control group) or the same diet with supplementation of 2 g of clofibrate per kg of diet (clofibrate group). In the clofibrate group, mRNA concentrations of various PPARα target genes involved in fatty acid utilization in liver and skeletal muscle were moderately up-regulated. Fat and energy content of the milk and gains of litters during the suckling period were not different between the control group and the clofibrate group.ConclusionIt is shown that treatment with clofibrate induces only a moderate up-regulation of PPARα target genes in liver and muscle of lactating sows and in turn might have limited effect on whole body fatty acid utilization. This may be the reason why clofibrate treatment did not influence milk fat content and gains of litters during the suckling period. Thus, the present study indicates that activation of PPARα induced either by native agonists such as dietary polyunsaturated fatty acids or a by negative energy balance might be largely uncritical in lactating sows with respect to milk production and litter gains in lactating sows.

The metabolic regulation of fenofibrate is dependent on dietary protein content in male juveniles of Nile tilapia (Oreochromis niloticus)

“…However, as most of other genes, the FATP isoforms have not been fully investigated in fish. In the HP group, fenofibrate decreased the HL content and increased the lipid-catabolism-related gene CPT1a and lipid-transport-related genes CD36 and FATP5, which partially agreed with previous studies on lipid-lowering effect of fibrates in yellow catfish, lactating sows and monkeys (13,28,29) . Nevertheless, fenofibrate also increased FAS and Srebp1c, the genes related to lipid synthesis in the HP group.…”

“…To limit the possible accumulation of excreted fenofibrate and its metabolites in water, all water was renewed by using stock water daily at 17.00 hours. Water temperature was maintained at 28…”

Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia

“…However, in sheep treated with 2-methyl-2-phenoxypropionic acid + 100 mL of glycerol-propylene glycol (Group B) and only with glycerol-propylene glycol (Group C), this increase was more precocious than in sheep treated only with 2-methyl-2-phenoxy-propionic acid (Group A), in accordance with Cal-Pereyra et al (2015b), who have previously reported a significant increase in glycaemia 12 h after treatment with glycerol-propylene glycol started. Propylene glycol is absorbed from the rumen at a rate of 40% per hour without being metabolized producing a rapid increase in blood glucose concentration at about 4 h after its administration (Herdt & Emery, 1992), which explains the precocious increase in glycaemia in groups B and C. 2-Methyl-2-phenoxy-propionic acid is a fibrate that regulates gene expressions involved in gluconeogenesis, but it is not a glucose precursor (Georgiadi & Kersten, 2012;Gessner et al, 2015), resulting in lower increase in glycaemia in Group A. Glycaemia values in the two groups including glycerol-propylene glycol (groups B and C) remained high for a longer time, which can be a consequence of slow glycerol degradation producing a high proportion of propionate, the main precursor of glucose via gluconeogenesis, resulting in a increase in glycaemia for a relatively long period (Rook, 2000;Cal-Pereyra et al, 2012). Considering another objective proposed in the treatment of this pathology is to restore the normal concentration of blood ketone bodies (Herdt & Emery, 1992), findings in this research showed a decrease in BHOB serum concentrations in all ewes of the three groups once the treatment started.…”

“…These activatable lipid nuclear receptors play an important role in the transcription and regulation of genes involved in lipid metabolism and energy homoeostasis (Chawla et al, 2001). PPARs can be activated also by fibrates or binders (Chawla et al, 2001;Michalik et al, 2006;Gessner et al, 2015). There are three types of nuclear receptors: PPARa, PPARb and PPARc distributed in different tissues with different specific functions (Michalik et al, 2006;Georgiadi & Kersten, 2012).…”

“…PPARa also participates in energy homoeostasis regulating the gene expression involved in hepatic gluconeogenesis, as they stimulate the synthesis of the phosphoenolpyruvate carboxykinase enzyme (Michalik et al, 2006;Georgiadi & Kersten, 2012;Gessner et al, 2015). The 2-methyl-2-phenoxypropionic acid is a PPAR-specific fibrate stimulant acting in the same way as natural bindings.…”