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M T Nakamura

Publications and source records attributed to M T Nakamura.

8 recordsLinked to original sources
PubMed1996

Increased hepatic delta 6-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 delta 6-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 delta 6-desaturase activity. Animals expressing the ovine growth hormone transgene had a 2.5-fold higher liver delta 6-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.

Adipose Tissue↗
PubMed1994

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.

Alcoholism↗
PubMed1993

The body composition and lipid metabolic effects of long-term ethanol feeding during a high omega 6 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.

Analysis of Variance↗
PubMed1993

Abnormal polyunsaturated lipid metabolism in the obese Zucker rat, with partial metabolic correction by gamma-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)

Adipose Tissue↗
PubMed1992

Reduced tissue arachidonic acid concentration with chronic ethanol feeding in miniature pigs.

The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ ethanol/kg body wt, and also five control pigs pair-fed the same amount of basal diet but with corn starch substituted for ethanol. After 12 mo, biopsy samples were taken, and tissue fatty acid profiles were analyzed. In the phospholipid fraction from the ethanol group there was a uniform decrease in arachidonic acid (AA) and an increase in oleic acid in liver, serum, and muscle. AA was consistently decreased in the triglyceride fractions of liver, serum and subcutaneous adipose of the ethanol group. Possible explanations for this general reduction in tissue AA with ethanol feeding include decreased activities of delta 6 and delta 5 desaturases, and a displacement of AA from lipid fractions by other fatty acids.

Adipose Tissue↗