Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows.

Insulin resistance in dairy cows.

Recent studies associate obesity and in- sulin resistance in horses with development of abnor- mal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor α (TNFα), IL1, and IL6 play direct roles in development of obesity-associated insulin resis- tance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relation- ships between obesity, inflammatory cytokines, and in- sulin sensitivity (IS) in the horse. Age was recorded and BCS and percent body fat (% FAT) were determined as measures of obesity in 60 mares. In addition, blood mRNA expression of IL1, IL6, and TNFα and circulat- ing concentrations of TNFα protein (TNFp) were deter- mined in each mare. Finally, fasted concentrations of insulin were determined, and IS was determined using the hyperinsulinemic, euglycemic clamp. Significant correlations between several variables provided evi- dence for the design of 4 population regression models to estimate relationships between measures of obesity, inflammatory factors, and IS in the sample population. The results of these analyses revealed that IS decreased as BCS and % FAT increased (P < 0.001) in the sample population. Additionally, increased IL1 (P < 0.05) and TNFp (P < 0.01) were associated with decreased IS. However, increased TNFα (P < 0.001) was associated with decreased IS only in mares 20 yr of age and older. Increased BCS and % FAT were associated with in- creased expression of TNFα (P = 0.053) and IL1 (P < 0.05), and increased TNFp (P < 0.05). Surprisingly, increased BCS and % FAT were associated with de- creased IL6 expression (P = 0.05) in mares <20 yr of age. Finally, evaluation of the influence of obesity and inflammatory cytokines on IS within the same model suggested that BCS and % FAT (P < 0.001) with TNFα (mRNA (P = 0.07) and protein (P < 0.05)) are inversely associated with IS independently of one another. Com- bined, these results provide the first evidence associat- ing obesity with increased inflammatory factors in the horse. Furthermore, the results suggest that an interre- lationship exists among obesity, inflammatory cytok- ines, and IS in the horse and emphasize the need for further studies to elucidate the nature of these rela- tionships.

https://www.paardenwelzijnscheck.nl/app/webroot/files/ckeditor_files/files/Voeding%20en%20Water/Vick%20et%20al.%20(2007)%20Relationships%20among%20inflammatory%20cytokines%2C%20obesity%2C%20and%20insulin%20sensitivity%20in%20the%20horse.pdf

Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse.

The nursery rhyme "Little Miss Muffet sat on a tuffet (small stool) eating her curds and whey. ..." is recognition of the fact that over the centuries "curds and whey", the two major components of cow's milk, have been widely accepted as part of a healthy diet. Milk provides complete nourishment for the neonate for six months from birth, containing factors that help develop various organ systems including the brain, immune system, and the intestine. Importantly it provides immune protection at a time when the neonates own immune system, though fully developed, is albeit immature. Many adult consumers include cow's milk as part of a healthy diet as it provides protein and essential nutrients, vitamins, and minerals, in particular calcium for strong bones. There is a growing appreciation that milk, and in particular whey, contains components that not only provide nutrition, but can also prevent and attenuate disease, or augment conventional therapies, when delivered in amounts that exceed normal dietary intakes. This paper reviews the emerging health properties of whey proteins and their clinical implications.

Emerging Health Properties of Whey Proteins and Their Clinical Implications

Bioactivity of β-lactoglobulin and α-lactalbumin—Technological implications for processing

Dairy cows undergo tremendous metabolic and physiological adaptations around parturition to support lactation. The liver is central to many of these processes, including gluconeogenesis and metabolism of fatty acids mobilized from adipose tis- sue. Fat accumulation may impair normal functions of the liver and increase ketogenesis, which in turn may predispose cows to other metabolic abnormalities. Several aspects of dietary management and body condition may alter these adaptations, affect dry matter intake, and increase or decrease susceptibility to periparturient health problems. Overfeeding energy dur- ing the dry period is a prominent risk factor. Considerable progress has been made in recent years in describing the adap- tive changes in the liver and other organs in normal and abnormal states, but this knowledge has not yet identified unequiv- ocally the key steps that might be compromised during development of metabolic disorders. The potential role of signaling compounds, such as the inflammatory cytokines released in response to environmental stressors, infectious challenge, and oxidative stress, in the pathogenesis of periparturient disease is under investigation. New techniques such as functional genomics, using cDNA or oligonucleotide microarrays, as well as proteomics and metabolomics, provide additional high- throughput tools to determine the effects of nutrition, management, or stressors on tissue function in development of dis- ease. Integrative approaches should be fruitful in unraveling the complex interactions of metabolism, immune activation, stress physiology, and endocrinology that likely underlie development of periparturient disease.

Physiological and pathological adaptations in dairy cows that may increase susceptibility to periparturient diseases and disorders

Effects of intramuscular fat deposition on the chemical composition, tenderness, and free amino acids (FAA) concentration of beef were studied using various classified carcasses of 21 Japanese Black (Wagyu) steers. The Beef Marbling Standard (BMS) No., judged on the market in 1998, and fat content, ranged from 2 to 10 and 4.8 to 39.0% in the M. longissimus thoracis, respectively. Moisture content was negatively correlated with the fat content (r =−0.98, P < 0.01). In contrast, protein content was relatively constant up to approximately 23% fat, corresponding to BMS No.4, and decreased as the fat content increased. Cooking loss was also constant up to approximately 28% fat, corresponding to BMS No.4, and markedly decreased with fat content increase. The beef in these cases were, however, classified into BMS No. around 9 and 11, respectively, according to the BMS model in 1988. A negative correlation was found between the shear-force value and the fat content (r =−0.83, P < 0.05). Most FAA concentrations on the wet weight of meat were correlated negatively with the fat content, except glutamine, and this negative relationship was still observed when the concentrations were recalculated on the basis of protein. These results indicate that higher marbling Wagyu beef (above approx. 23% fat) would have an extremely lower content of protein, which would partly explain the lower cooking loss and FAA with fat increase. In addition, some other reasons not relating to protein content (e.g. high fat content preventing the breakdown of protein to FAA) seem to explain the negative correlation between fat and FAA.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1740-0929.2007.00424.x

Effects of intramuscular fat deposition on the beef traits of Japanese Black steers (Wagyu)

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

Four experiments were conducted to clarify the effect of intravenous (i.v.) administration of recombinant bovine tumor necrosis factor alpha (rbTNF) on selected metabolites and on hormone secretion in Holstein heifers (n = 6; 347.0 kg average BW). In Exp. 1, rbTNF was injected at three dosage levels in a Latin square; 0 (CONT), 2.5 (TNF2.5), or 5.0 (TNF5) microg/kg BW. Plasma glucose and triglyceride concentrations were at first elevated (P < .05) by rbTNF treatment and then were decreased (P < .05) by TNF2.5 and TNF5. Plasma NEFA concentrations were increased (P < .05) in rbTNF-treated groups. The injection of rbTNF resulted in an increase in plasma insulin levels (P < .05 with TNF5) during the period between 2 and 24 h, except for the period between 6 and 8 h, after the treatment. In Exp. 2, 3, and 4, each heifer received i.v. injections of glucose (.625 mM/kg BW) + rbTNF (5 microg/kg) or glucose + saline (10 mL) (Exp. 2), insulin (0.2 U/kg) + rbTNF or insulin + saline (Exp. 3), and GHRH (0.25 microg/kg) + rbTNF or GHRH + saline (Exp. 4) at 1-wk intervals. In Exp. 2, rbTNF inhibited (P < .05) glucose-stimulated insulin secretion during the initial phase. Thereafter, plasma insulin was higher (P < .01) with the glucose + rbTNF treatment than with the glucose + saline treatment. Treatment with rbTNF inhibited the insulin-stimulated glucose utilization (Exp. 3) and GHRH-stimulated GH secretion (Exp. 4) during the initial phase. These results suggest that rbTNF directly and(or) indirectly affects the intermediary metabolism and hormone secretion in Holstein heifers.

Administration of recombinant bovine tumor necrosis factor-alpha affects intermediary metabolism and insulin and growth hormone secretion in dairy heifers.

Endotoxin induces marked changes in lipid metabolism via its effects on cytokines. To evaluate the role of tumor necrosis factor-alpha (TNF) in mediating changes of lipid metabolism in ruminants, we performed a crossover saline-controlled study in Holstein heifers (n = 8; 394.0 kg average BW), investigating the metabolic effects of a single intravenous administration of recombinant bovine TNF (rbTNF, 5.0 microg/kg). Blood samples were taken from a jugular vein at 0 (1100, just before injection), 0.5, 6, 12, and 24 h after each treatment. Dry matter intake in the heifers was not affected by single administration of the rbTNF. The rbTNF produced early as well as later hypertriglyceridemia (P < 0.05) in dairy heifers. The rbTNF also induced an early and sustained rise (P < 0.05) in the plasma NEFA concentration. Plasma retinol concentration was decreased (P < 0.05) at 24 h after rbTNF injection, whereas the a-tocopherol concentration was not significantly affected by rbTNF treatment. At 0.5 and 24 h, there was an increase (P < 0.05) in the plasma concentration of the very-low-density lipoprotein (VLDL) fraction in rbTNF-treated heifers. Between 6 and 24 h after rbTNF treatment, concentration of the low-density lipoprotein fraction declined (P < 0.05) but the high-density lipoprotein fraction was not altered in the rbTNF-treated heifers. These results indicate that TNF produces a hypertriglyceridemic response associated with an increase of the VLDL fraction and a disturbance of retinol metabolism in dairy heifers.

Alterations in lipid metabolism induced by recombinant bovine tumor necrosis factor-alpha administration to dairy heifers.

OBJECTIVE To investigate the effects of long-term administration of recombinant bovine tumor necrosis factor-alpha (rbTNF) on plasma glucose and growth hormone concentrations, and to determine whether treatment with rbTNF causes insulin resistance in steers. ANIMALS 5 steers treated with rbTNF and 5 steers treated with saline (0.9% NaCl) solution (control). PROCEDURES In experiment 1, rbTNF (5.0 microg/kg of body weight) or saline solution (5 ml) was administered SC daily for 12 days. Blood samples were obtained before treatment, and plasma was harvested for determination of glucose, insulin, and growth hormone (GH) concentrations. In experiment 2, insulin, glucose, or growth hormone-releasing hormone (GHRH) was administered IV on days 7, 9, and 11, respectively, after initiation of rbTNF or saline treatment in experiment 1. Plasma glucose and insulin concentrations were measured before and at various times for 4 hours after insulin or glucose administration. Plasma GH concentrations were measured at various times for 3 hours after GHRH administration. RESULTS In experiment 1, administration of rbTNF resulted in hyperinsulinemia without hypoglycemia and decreased plasma GH concentrations. In experiment 2, plasma glucose concentrations were higher in steers treated with rbTNF and insulin than in controls. Plasma GH concentrations were lower in steers treated with rbTNF and GHRH than in controls. CONCLUSIONS AND CLINICAL RELEVANCE Prolonged treatment with rbTNF induced insulin resistance and inhibited GHRH-stimulated release of GH in steers. Results indicate that rbTNF is a proximal mediator of insulin resistance and inhibits release of GH during periods of endotoxemia or infection.

Hiroyuki Shingu

Papers

Effects of intramuscular fat deposition on the beef traits of Japanese Black steers (Wagyu)

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

Administration of recombinant bovine tumor necrosis factor-alpha affects intermediary metabolism and insulin and growth hormone secretion in dairy heifers.

Alterations in lipid metabolism induced by recombinant bovine tumor necrosis factor-alpha administration to dairy heifers.

Effects of long-term administration of recombinant bovine tumor necrosis factor-alpha on glucose metabolism and growth hormone secretion in steers.