Shiro Kushibiki

Insulin resistance induced in dairy steers by tumor necrosis factor alpha is partially reversed by 2,4–thiazolidinedione

The aim of this study was to determine whether 2,4-thiazolidinedione (2,4-TZD) influences the effects of peripheral insulin action in steers given recombinant bovine tumor necrosis factor (TNF) alpha (rbTNF). Steers were treated once daily for 9 d (d0 - d8) with either s.c. injection of rbTNF (2.5 microg/kg), rbTNF + i.v. injection of 2,4-TZD (2.0 mg/kg), or s.c. injection of saline (control). The plasma glucose, NEFA, and insulin concentrations in the rbTNF-treated group increased compared to those in the control and rbTNF + 2,4-TZD groups, whereas glucagon concentration decreased. A single i.v. injection of insulin (0.2 U/kg), glucose (112.5 mg/kg), or growth hormone (GH)-releasing hormone (GHRH) (0.25 microg/kg) was performed on d4, d6, and d8, respectively. In the insulin challenge, the net area under the glucose curve (AUC) was smaller in the rbTNF group than in the control and rbTNF + 2,4-TZD groups. In the glucose challenge, the net insulin AUC was smaller in rbTNF + 2,4-TZD group than in rbTNF group. In the GHRH challenge, there was no difference in GH responses to GHRH between the rbTNF and rbTNF + 2,4-TZD groups, respectively. We conclude that 2,4-TZD treatment partially reverses the impairment of peripheral insulin action caused by rbTNF injection in steers.

Effect of β-lactoglobulin on plasma retinol and triglyceride concentrations, and fatty acid composition in calves

Beta-lactoglobulin (beta-lg) is the main protein of ruminant milk whey. Although beta-lg can bind in vitro to a variety of hydrophobic substrates, mainly retinol and long-chain fatty acids, its physiological function is still unknown. In Exp. 1, we investigated the effect of beta-lg on the plasma retinol concentration in preruminant calves. Holstein male calves (n = 20) were fed Holstein whole milk at 40 g/kg body weight (BW) plus vitamin A acetate (500,000 i.u.) with or without beta-lg (0.4 g/kg BW). The plasma retinol concentration of 10-d-old calves was greater (P < 0.05) in the beta-lg-fed group) than in the control group during the period from 8 to 12 h and at 24 h after the feeding. The postprandial change of plasma retinol in 40-d-old calves fed milk with beta-lg was higher (P < 0.05) than that in the control calves only at 12 h after the feeding. In Exp. 2, Holstein male calves (n = 18) were used to investigate the effect of beta-lg on plasma triglyceride concentration and fatty acid composition. Calves were fed Holstein whole milk at 40 g/kg BW plus milk fat prepared from whole milk at 2 g/kg BW with or without beta-lg (0.4 g/kg BW). Plasma triglyceride concentration at age 10 d was higher (P < 0.05) in the beta-lg-fed group than in the controls during the periods from 1 to 2 h and from 7 to 11 h after the feeding. At age 40 d, plasma triglyceride in the beta-lg-fed group was higher (P < 0.05) than in the control group only at 9 h. Ratios of palmitic, stearic, and oleic acids to total plasma lipids were higher (P < 0.05) in the calves fed beta-lg milk than in the control calves at age 10 d. These results suggest that beta-lg enhances the intestinal uptake of retinol, triglyceride, and long-chain fatty acids in preruminant calves.

Profiles of growth hormone and insulin secretion, and glucose response to insulin in growing Japanese Black heifers (beef type) : comparison with Holstein heifers (dairy type)

Nine Japanese Black and 10 Holstein heifers ranging from 1 week (wk) to 18 months (mo) old received a single bolus intravenous injection of GH-releasing factor (GRF, 0.25-microg/kg BW), glucose (112.5-mg/kg BW) or insulin (0.2-U/kg BW) at various stages through 18 mo of age. The GH secretory response to exogenous GRF in Japanese Black heifers was lower than that in Holstein heifers at all stages of growth. While insulin secretory function was not very different in both breeds from 1 to 12 mo of age, the insulin response was much higher in Japanese Black heifers than in Holstein heifers after sexual maturation. The degree of decrease in plasma glucose following insulin injection was similar in both breeds at each stage of growth. It is concluded that compared with Holstein heifers, Japanese Black heifers have lower GH and higher insulin secretory functions, and that the two breeds have similar glucose response to insulin.

Tumor necrosis factor‐α‐induced inflammatory responses in cattle

Tumor necrosis factor-alpha (TNF-α) is recognized as a cytokine because of its involvement in inflammation-mediated biological defense functions. Although TNF-α is primarily produced by macrophages, it is also produced by other cells, including lymphocytes, Kupffer cells, natural killer cells and adipocytes. While TNF-α has diverse immune system functions, including antitumor activity, antimicrobial activity and mediation of inflammation, it also regulates a number of physiological functions, including appetite, fever, energy metabolism and endocrine activity. Factors such as viruses, parasites, other cytokines, and endotoxins induce TNF-α production. In combination with other cytokines, TNF-α plays a clinically important role in cattle by mediating immune inflammatory responses such as mastitis and endotoxic shock. It has been reported that cytokines such as TNF-α are involved in metabolic disease such as acidosis. On the other hand, several data suggest that lactoferrin (LF) acts to prevent the release of a number of inflammatory mediators from various activated cells, and further suggest that the prophylactic effect of LF involves inhibition of cytokine production, including TNF-α, that are principal mediators of the inflammatory response leading to death from toxic shock. This review discusses the role of TNF-α in pathological conditions in cattle, including infections and metabolic diseases caused by perturbation of metabolism and endocrine functions.

Effect of cellooligosaccharide or synbiotic feeding on growth performance, fecal condition and hormone concentrations in Holstein calves

We investigated the effect of cellooligosaccharide (CE) or a combination of dextran and Lactobacillus casei ssp. casei strain JCM1134(T) (synbiotic; SB) feeding on growth performance, fecal condition and hormone concentrations in Holstein calves. Fifty-two female Holstein calves were randomly assigned to three treatment groups: CE feeding group (n = 16), SB feeding group (n = 18), and control group (n = 18). Body weight at 90 days of age, as well as daily body weight gain (DG) and feed efficiency after weaning to 90 days of age were greater (P < 0.05) in the CE feeding group than in the control group. The total fecal score tended to be lower (P < 0.1) in the SB feeding group than in the control group. Plasma insulin concentration was higher (P < 0.05) in the CE feeding group than in the control group at 90 days of age. Our results indicate that CE feeding improved DG and feed efficiency in calves. On the other hand, there was less effect on growth performance and fecal Escherichia coli counts in calves fed SB.

Ingestion of medium chain fatty acids by lactating dairy cows increases concentrations of plasma ghrelin.

The purpose of this study was to elucidate the effects of medium-chain fatty acids (MCFAs) on plasma ghrelin concentration in lactating dairy cows. Five early-lactating Holstein cows were randomly assigned to 2 dietary treatments in a crossover design with 2-wk periods. Treatments consisted of diets supplemented or not (control) with calcium salts of MCFAs (MCFA-Ca; 1.5% dry matter). Plasma hormone and metabolite concentrations in blood samples taken from the jugular vein were measured on the morning of feeding on day 14 of each period. Dry matter intake, milk protein, and lactose content of cows fed the MCFA-Ca diet were decreased compared with controls, but with no change in milk yield. Plasma ghrelin concentrations were higher in cows fed the MCFA-Ca diet; however, no significant effect was found on glucagon-like peptide-1 concentrations in plasma. Plasma insulin concentrations decreased, but plasma glucagon concentrations remained unchanged in cows fed the MCFA-Ca diet. The concentrations of nonesterified FAs, total cholesterol, and β-hydroxybutyrate in plasma increased in these cows. In conclusion, dietary MCFAs increase the plasma ghrelin concentrations in lactating dairy cows.

Breed differences in growth hormone and insulin secretion between lactating Japanese Black cows (beef type) and Holstein cows (dairy type).

This study was performed to clarify the levels of growth hormone (GH) and insulin (INS) secretions and the glucose response to INS during lactation in a representative beef breed in Japan, Japanese Black cows, and to compare them with their counterparts in a dairy breed, Holstein cows. Six Japanese Black and seven Holstein primiparous cows received a single intravenous injection of GH-releasing factor (GRF; 0.25 microg/kg), glucose (112.5 mg/kg), or INS (0.2 U/kg) from late pregnancy (2 weeks antepartum) to mid-lactation (6 months postpartum). Japanese Black cows had one-tenth of the total milk yield of Holstein cows during lactation, and significantly lower GRF-induced GH and higher glucose-induced INS secretions than Holstein cows at all stages. In Japanese Black cows, even with lactation, these secretions remained essentially unchanged, whilst Holstein cows showed higher GH and lower INS secretions after the onset of lactation as compared with cows in late pregnancy. Both breeds had similar glucose response to INS at the respective stages. These results suggest that, during lactation, Japanese Black cows may minimize the catabolic effects of GH and sustain the anabolic effects of INS, in contrast with Holstein cows, but have similar ability to inhibit INS-mediated glucose utilization in peripheral tissues to Holstein cows.

Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows

Our objective was to determine the effects of calcium salts of long-chain fatty acids (CLFAs) and rumen-protected methionine (RPM) on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide, and pancreatic hormones in lactating cows. Four Holstein cows in midlactation were used in a 4 by 4 Latin square experiment in each 2-wk period. Cows were fed corn silage-based diets with supplements of CLFAs (1.5% added on dry matter basis), RPM (20 g/d), CLFAs plus RPM, and without supplement. Jugular blood samples were taken from 1 h before to 2 h after morning feeding at 10-min intervals on day 12 of each period. CLFAs decreased dry matter intake, but RPM did not affect dry matter intake. Both supplements of CLFAs and RPM did not affect metabolizable energy intake and milk yield and composition. Plasma concentrations of NEFAs, triglyceride (TG), and total cholesterol (T-Cho) were increased with CLFAs alone, but increases of plasma concentrations of TG and T-Cho were moderated by CLFAs plus RPM. Calcium salts of long-chain fatty acids increased plasma ghrelin concentration, and the ghrelin concentration with CLFAs plus RPM was the highest among the treatments. Plasma concentrations of glucagon-like peptide-1, glucagon, and insulin were decreased with CLFAs, whereas adding RPM moderated the decrease of plasma glucagon concentration by CLFAs. These results indicate that the addition of methionine to cows given CLFAs increases plasma concentrations of ghrelin and glucagon associated with the decrease in plasma concentrations of TG and T-Cho.

Effects of amino acids infused into the vein on ghrelin-induced GH, insulin and glucagon secretion in lactating cows

To investigate the effects of amino acids on ghrelin-induced growth hormone (GH), insulin and glucagon secretion in lactating dairy cattle, six Holstein cows were randomly assigned to two infusion treatments in a cross-over design. Mixture solution of amino acids (AMI) or saline (CON) was continuously infused into the left side jugular vein via catheter for 4 h. At 2 h after the start of infusion, synthetic bovine ghrelin was single injected into the right side jugular vein through the catheter. Ghrelin injection immediately increased plasma GH, glucose and non-esterified fatty acids (P<0.05) with no difference between both treatments. Additionally, plasma insulin and glucagon concentrations were increased by ghrelin injection in both treatments. The peak value of plasma insulin concentration was greater in AMI compared with CON (P<0.05). Plasma glucagon concentration showed no difference in the peak value reached at 5 min between both treatments, and then the plasma levels in AMI compared with CON showed sustained higher values (P<0.05). After plasma glucose concentration reached the peak, the decline was greater in AMI compared with CON (P<0.05). These results showed that the increased plasma amino acids may enhance ghrelin action which in turn enhances insulin and glucagon secretions in lactating cows.

Proteome analysis of whole and water-soluble proteins in masseter and semitendinosus muscles of Holstein cows

To assess both quantitative and qualitative differences between the slow- and fast-type muscles, masseter (slow) and semitendinosus (fast) from four Holstein cows were analyzed by two-dimensional difference gel electrophoresis (2D DIGE) and mass spectrometry. The proteome analysis identified 27 spots as 20 proteins in the whole protein fraction extracted with 8 mol/L urea solution, and 16 spots were identified as 11 proteins in the water-soluble protein fraction. Two slow-type myofibrillar proteins (myosin light chain-1 slow-b and myosin light chain-2 slow), and aconitase-2 mitochondria were present at higher levels in the masseter muscle (P < 0.05). Four fast-type myofibrillar proteins (myosin light chain-1 fast, myosin light chain-2 fast, myosin light chain-3 fast and tropomyosin-1), and three enzymes of glycolytic pathway (enolase-3, aldolase-A and triosephosphate isomerase), were present at higher levels in the semitendinosus muscle (P < 0.05). Our proteome analysis showed that the composition of sarcoplasmic proteins as well as myofibrillar proteins was clearly different between slow- and fast-type muscles.