Anna B. Tang

Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol.

This study investigated the mechanism by which chronic ethanol feeding reduces arachidonate and other highly unsaturated fatty acids in pig liver phospholipids. Five micropigs were fed a diet providing 89 kcal/kg body wt for 12 mo, with ethanol and fat as 40 and 34% of energy, respectively. Five control pigs were pairfed corn starch instead of ethanol. The activities of delta 6 and delta 5 desaturases (expressed as microsomal conversion of precursor to product) in liver from ethanol-fed pigs were reduced to less than half that of controls, whereas the activity of delta 9 desaturase was unaffected in the ethanol group. delta 5 Desaturase activity showed positive correlation with the abundance of its products in liver total phospholipids and microsomes in the ethanol group, but not in the controls. Correlation between delta 6 desaturase activity and its products showed similar pattern to that of delta 5 desaturase, but did not reach statistical significance. No difference was observed between the two groups in coenzyme A concentration in the liver. These results suggest that the selective reduction of delta 6 and delta 5 desaturase activities, not the microsomal electron transport system, are directly responsible for the altered profile of liver phospholipids.

Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by γ-linolenic acid administration

Below-normal proportions of phospholipid (PL) arachidonic acid (20:4 omega 6) have been reported in serum from obese humans and in liver from obese Zucker rats. This implies an abnormality of 20:4 omega 6 formation from linoleic acid (18:2 omega 6), possibly in the delta 6 desaturase step, or alternatively an abnormality in the catabolism or distribution of arachidonate. We previously speculated that a reduced proportion of 20:4 omega 6 in hepatic PL could contribute to the etiology of genetic obesity. Providing 18:3 omega 6 would bypass delta 6 desaturase and possibly normalize hepatic PL 20:4 omega 6. Therefore weanling Zucker rats were given free access to a defined diet (11% of energy as soy oil) and gavaged daily with 100 microL of either black currant oil concentrate ([BCO] 8% 18:2 omega 6 and 70% 18:3 omega 6) or soy oil ([Soy] 55% 18:2 omega 6 and < 0.1% 18:3 omega 6). Groups of eight lean and eight obese animals were randomized to receive Soy or BCO in a 2 x 2 design; 10 obese and 10 lean rats were fed a stock diet (nongavaged reference). All groups of lean rats had identical weight gain; food intake for Soy lean and BCO lean did not differ. The obese reference animals and Soy obese animals did not differ in weight gain. However, BCO obese animals ate less food (P < .06), gained less weight (P < .0001), and had lower percent body fat (P < .05) compared with the Soy obese animals. The fatty acid constituents from serum, liver, and adipose tissue showed marked differences between lean and obese animals. Hepatic PL 20:4 omega 6 was lower in Soy obese than in lean (P < .002), but was normalized by BCO gavage (diet effect, P < .007). The paucity of hepatic PL 20:4 omega 6 was not due to reduced desaturase activity, as the proportions of other desaturase products (20:3 omega 6, 20:3 omega 9, 20:5 omega 3) were significantly elevated in Soy obese rat liver and serum. Serum and hepatic cholesteryl ester 20:4 omega 6 levels were elevated in obese versus lean rats (P < .02 and P < .0001), indicating abnormal arachidonate distribution in the obese Zucker rat. Because BCO selectively reduced weight gain and percent body fat in obese Zucker rats, our results imply a role for abnormal omega 6 fatty acid metabolism in the etiology of Zucker obesity.(ABSTRACT TRUNCATED AT 400 WORDS)

Reduced adipose 18∶3ω3 with weight loss by very low calorie dieting

The human undergoing rapid and sustained weight loss by very low calorie dieting (VLCD) derives the majority of daily energy needs from adipose fatty acids. To evaluate the rates of metabolic utilization of individual fatty acids in humans, two groups of adult women outpatients were studied during major weight loss by VLCD. The diets used were either food or formula, providing the recommended dietary allowance for minerals and vitamins, with fat contents of 2–20 g/d. Group 1 consisted of 10 subjects [initial body mass index (BMI) 32.7, 157% of ideal body weight (IBW)] with a mean loss of 17.7 kg in 3–5 months. Group 2 consisted of 14 subjects (initial BMI 36.7, 167% of IBW) with a mean loss of 25.6 kg in 4–5 months. Adipose tissue biopsies were obtained by needle aspiration from Group 1 before and after weight loss and from Group 2 before, at the midpoint, and after weight loss. With weight loss in Group 1, the adipose tissue content of 18∶1ω9, 18∶2ω6, and 20∶4ω6 did not change, but 18∶3ω3 fell (0.67 to 0.56 wt%, p<0.0001) as did 20∶5ω3 (0.08 to 0.05, p<0.01). Adipose tissue 22∶6ω3 rose from 0.03 to 0.07 (p<0.01). In Group 2, only 18∶3ω3 showed a change, falling from 0.71 to 0.69 to 0.59 wt% across weight loss (p=0.03 by analysis of variance). We conclude that the major fatty acids are oxidized in proportion to their composition in adipose triglyceride. The significant reduction in the concentration of 18∶3ω3 during weight loss is unique among fatty acids. Its accelerated removal from adipose tissue indicates either a preferential step in β-oxidation or a defined need during supplemented fasting which exceeds its rate of provision from adipose stores.

Preferential reduction in adipose tissue α-linolenic acid (18∶3ω3) during very low calorie dieting despite supplementation with 18∶3ω3

We have previously reported that the relative content of 18∶3ω3 in adipose triglyceride (TG) of women was reduced following major weight loss while on a very low calorie diet (VLCD). In an attempt to prevent this loss of 18∶3ω3 reserves, we have tested two VLCD supplemented with varying amounts of 18∶3ω3. The formula (FORM) and food VLCD (2.1–3.0 MJ or 500–700 kcal/d) contained 20 g/d of fat and provided the recommended dietary allowance for minerals and vitamins. FORM subjects (Group 1) were 5 women [initial body mass index (BMI) of 36.8, 168% ideal body weight (IBW) who received 20 g/d of canola oil (1.6 g 18∶3ω3). Their mean weight loss was 23.9 kg in a 4–5 mon period. Food VLCD subjects (Group 2) were 6 women (BMI 33.9, 155% IBW) supplemented with 2 g/d of linseed oil (1.1 g 18∶3ω3). Their mean weight loss was 17.4 kg in a 2–3 mon period. Needle biopsies of adipose tissue were obtained from Group 1 before, at midpoint and after weight loss; and from Group 2 before and after weight loss. The adipose TG and serum (Group 1) were separated and their fatty acid composition determined by thin-layer and gas chromatography. In Group 1, adipose 18∶3ω3 fell from 0.65 to 0.59 wt%, then to 0.52 wt% during weight loss. In Group 2, it fell from 0.77 to 0.64 wt%. The fall in adipose 18∶3ω3 with weight loss was significant atP=0.01 (Group 1) andP<0.01 (Group 2). There were no differences between responses to the 1.1 g/d or 1.6 g/d 18∶3ω3 supplements. The relative content of 18∶3ω3 in serum free fatty acids from Group 1 was reduced after major weight loss. Thus, in both groups the ω3 supplementation did not help to maintain adipose tissue 18∶3ω3 during rapid weight loss, and its decrement may affect circulating lipid pools. As adipose 18∶2ω6 did not change with weight loss, this reduction in the ratio of ω6 precursor to ω3 precursor could eventually alter the balance of their products as well.

Increased hepatic Δ6-Desaturase activity with growth hormone expression in the MG101 transgenic mouse

Growth hormone (GH) has many metabolic effects, but its mechanism(s) of action are not fully understood. We studied the short-term effects of endogenously produced GH on liver Δ6-desaturase activity and adipose and liver lipid fraction fatty acid composition in transgenic mice. MG101 transgenic mice ages 73–114 d received zinc to activate the ovine GH transgene for 7 d. Nontransgenic littermates, used as controls, also received zinc. Liver lipids were fractionated into phospholipids (PL), cholesteryl esters, and triglycerides (TG), and retroperitoneal adipose fractionated into PL and TG for fatty acid analysis. Liver microsomes were assayed for Δ6-desaturase activity. Animals expressing the ovine growth hormone transgene had a 2.5-fold higher liver Δ6-desaturase activity than controls. Arachidonate and docosahexaenoate were significantly higher in liver PL of GH transgenic animals compared to controls, but both were decreased in adipose PL in the GH animals. We conclude that increased production of GH affects both production and organ distribution of highly unsaturated fatty acids. The changes in arachidonate in various lipid pools following transgene expression may mediate the systemic actions of GH.

The body composition and lipid metabolic effects of long-term ethanol feeding during a high ω6 polyunsaturated fatty acid diet in micropigs☆☆☆

Our previous research with miniature pigs has shown that long-term ethanol feeding with a low-fat diet decreases arachidonic acid (20:4 omega 6) levels in multiple tissues, but we did not find significant liver pathology. In this study, we investigated the effect of ethanol feeding with high dietary linoleic acid (18:2 omega 6) on tissue fatty acid (FA) profiles and body composition. Five Yucatan micropigs were fed 370 kJ (89 kcal)/kg body weight of a diet containing ethanol and fat as 40% and 34% of energy, respectively; five control pigs were pair-fed corn starch in place of ethanol. Corn oil, 61% 18:2 omega 6, supplied most of the dietary fat. Liver biopsies were performed at baseline (n = 2 per group) and at three other time points (n = 5 per group). Phospholipid (PL) FA levels were measured by thin-layer and gas chromatography. Body composition was analyzed by underwater weighing of carcasses. Body composition analysis demonstrated a marked reduction of carcass fat in the ethanol group, but no significant reduction of carcass lean weight after 12 months. In liver PLs, the ethanol group showed decreased 20:4 omega 6 and docosahexaenoic acid (22:6 omega 3) after 1 month. While the decreased 20:4 omega 6 remained constant after 1 month, 22:6 omega 3 showed a progressive decrease up to 12-months, resulting in a continuous decrease of the omega 3/omega 6 FA ratio. This slowly progressive decrease in the omega 3/omega 6 ratio in liver PLs with ethanol feeding may have enhanced the inflammatory response in the liver, contributing to liver pathology. Body composition results indicate marked wasting of energy in the ethanol group.