David R. Glimm

Trans-11 Vaccenic Acid Dietary Supplementation Induces Hypolipidemic Effects in JCR:LA-cp Rats

Trans-11 vaccenic acid [VA; 18:1(n-9)] is a positional and geometric isomer of oleic acid and is the precursor to conjugated linoleic acid (CLA) in humans. Despite VA being the predominant trans monoene in ruminant-derived lipids, very little is known about its nutritional bioactivity, particularly in conditions of chronic metabolic disorders, including obesity, insulin resistance, and/or dyslipidemia. The aim of this study was to assess the potential of VA to improve dyslipidemia, insulin sensitivity, or inflammatory status in obese and insulin-resistant JCR:LA-cp rats. The obese rats and age-matched lean littermates were fed a control diet or a control diet supplemented with 1.5% (wt:wt) VA for a period of 3 wk. The incorporation of VA and subsequent conversion to CLA in triglyceride was measured in adipose tissue. Glucose and insulin metabolism were assessed via a conscious adapted meal tolerance test procedure. Plasma lipids as well as serum inflammatory cytokine concentrations were measured by commercially available assays. VA supplementation did not result in any observable adverse health effects in either lean or obese JCR:LA-cp rats. After 3 wk of feeding, body weight, food intake, and glucose/insulin metabolism did not differ between VA-supplemented and control groups. The incorporation of VA and CLA into adipose triglycerides in obese rats fed VA increased by 1.5-fold and 6.5-fold, respectively, compared with obese rats fed the control diet. The most striking effect was a 40% decrease (P < 0.05) in fasting triglyceride concentrations in VA-treated obese rats relative to obese controls. Serum Il-10 concentration was decreased by VA, regardless of genotype (P < 0.05). In conclusion, short-term dietary supplementation of 1.5% VA did not result in any detrimental metabolic effects in JCR:LA-cp rats. In contrast, dietary VA had substantial hypo-triglyceridemic effects, suggesting a new bioactivity of this fatty acid that is typically found in ruminant-derived food products.

Trans-11 Vaccenic Acid Reduces Hepatic Lipogenesis and Chylomicron Secretion in JCR:LA-cp Rats

Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid concentrations, as well as the serum haptoglobin concentration, were all lower in obese rats fed the VA diet compared with obese controls (P < 0.05). In addition, there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area under the curve (P < 0.05) for VA-treated obese rats compared with obese controls. The hepatic TG concentration and the relative abundance of fatty acid synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA-treated group compared with obese controls. Following acute gastrointestinal infusion of a VA-triolein emulsion in obese rats that had been fed the control diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by 30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In conclusion, chronic VA supplementation significantly improved dyslipidemia in both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways.

Grazing cows are more efficient than zero-grazed and grass silage-fed cows in milk rumenic acid production.

Six rumen-cannulated Holstein cows in early lactation were assigned to 3 treatments: grazing (G), zero-grazing (ZG), and grass silage (GS) harvested from the same perennial rye grass sward in a 3 x 3 Latin square design with three 21-d periods. The objectives of this study were to investigate the underlying mechanisms for the reported elevation in milk rumenic acid (RA) concentration associated with G compared with ZG and GS, and to identify the important variables contributing to the milk RA response. Grazing animals were offered 20 kg of dry matter/cow per day; indoor animals were offered ad libitum grass or silage. A concentrate at a rate of 3 kg/d was also offered to all cows. Rumen, plasma, and milk samples were collected in the third week of each period. Data were analyzed by the MIXED procedure of SAS. Dry matter intakes were less for GS with no difference between G and ZG. Milk yield was greater for G than for ZG or GS. Milk fat and protein contents were less for GS with no difference between G and ZG. The combined intake (g/d) of linoleic and linolenic (18:3n-3) acids was different across the treatments (G: 433; ZG: 327; and GS: 164). Rumen pH was less for G with no difference between ZG and GS. Concentrations of volatile fatty acids and ammonia nitrogen in rumens were not different across the treatments. Wet rumen fill was less for G with no difference between ZG and GS. Vaccenic acid concentrations were different across the treatments in rumen (G: 12.30%, ZG: 9.31%, and GS: 4.21%); plasma (G: 2.18%, ZG: 1.47%, and GS: 0.66%) and milk (G: 4.73%, ZG: 3.49%, and GS: 0.99%). Milk RA concentrations were greater for G (2.07%) than for ZG (1.38%) and GS (0.54%). Milk desaturase index based on the ratio cis-9-14:1/14:0 was not different across the treatments. Milk RA yield per 100 g of linoleic acid and linolenic acid intake (efficiency) was 2.23, 1.50, and 0.62 g in G, ZG, and GS, respectively, suggesting that G cows were more efficient than ZG and GS cows in milk RA production. Stepwise regression analysis of a group of variables revealed that plasma vaccenic acid accounted for 95% of the variation in milk RA production. Milk desaturase index did not enter into the model. Overall findings suggest that substrate intake influenced milk RA production but it was not the only factor involved. There were differences in efficiency of milk RA production, which appears to depend on the factors regulating ruminal vaccenic acid production and its supply to the mammary tissue.

Influence of stage of lactation on glucose and glutamine metabolism in isolated enterocytes from dairy cattle

Pathways of glutamine and glucose metabolism in early-, mid-, and late-lactation dairy cows were evaluated by in vitro incubations of enterocytes for 2 hours with [U-14-C]glutamine and [U-14C]glucose. Enterocytes from early-lactation cows produced greater amounts of CO2 from glutamine in concentrations that ranged from 2 to 8 mmol/L than enterocytes from either mid- or late-lactation cows. Enterocytes from early-lactation cows also produced greater amounts of CO2 from 4 and 6 mmol/L glucose than enterocytes from either mid- or late-lactation cows. Glutamine was metabolized via glutaminolysis mainly to ammonia, alanine, aspartate, glutamate, and CO2, and more of these products were produced in enterocytes from early-lactation cows than from pooled mid- and late-lactation (PML) cows. Glucose was metabolized mainly to lactate, as compared with pyruvate and CO2. Lactate and CO2 production were both greater in enterocytes from early-lactation cows than from PML cows. Glutamine as the sole substrate accounted for all the energy requirements of enterocytes from early-lactation cows but contributed only 31% in the presence of glucose. Similarly, glucose accounted for all the energy requirements of enterocytes from early-lactation cows and contributed 69% in the presence of glutamine. In enterocytes from all cows, the rate of adenosine triphosphate (ATP) production was greater in the presence of both glucose and glutamine compared with that in the presence of either substrate alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of feeding or abomasal infusion of canola oil in Holstein cows. 2. Gene expression and plasma concentrations of cholecystokinin and leptin

We determined the relative importance of cholecystokinin (CCK), leptin, and fatty acid concentrations in plasma in mediating the satiety effects of supplemental fat in lactating cows. Five ruminally and duodenally cannulated Holstein cows in late lactation were used in a 3 x 5 incomplete Latin square design with three treatments: 1) CONTROL: basal diet (CON), 2) CONTROL+supplementation of canola oil at 1 kg/d in the feed (FED) and 3) CONTROL+abomasal infusion of canola oil at 1 kg/d (INF). Relative to CON, feed intake was reduced by INF but not by FED. We provide evidence that both FED and INF treatments stimulated CCK gene expression in the duodenum and elevated plasma CCK concentrations. However, our results did not support a role for CCK in mediating satiety through an endocrine mechanism of action. We speculate that CCK might be acting either through paracrine and/or neurocrine routes to influence feed intake in cattle. Both FED and INF had no effect on the mRNA abundance of leptin, lipoprotein lipase, or acetyl-CoA carboxylase in adipose tissue. Plasma concentrations of leptin, insulin and IGF-I were not altered by FED or INF, indicating that these signals may not be involved in mediating short-term hypophagic effects of dietary fat. Plasma concentrations of 18:1n-9 and 18:2n-6 were significantly greater for INF than for FED or CON. We conclude that the hypophagic effects of supplemental fat in cattle depend on the amount of unsaturated fatty acids reaching the intestine and that this satiety effect is mediated through CCK, oleic acid and (or) linoleic acid, but leptin is not involved.