This brief review focuses on the transcriptional regulation of liver carnitine palmitoyltransferase I (L-CPT I) by pancreatic and thyroid hormones and by long-chain fatty acids (LCFA). Both glucagon and 3,3',5-tri-iodothyronine (T(3)) enhanced the transcription of the gene encoding L-CPT I, whereas insulin had the opposite effect. Interestingly, the transcriptional effect of T(3) required, in addition to the thyroid-responsive element, the co-operation of a sequence located in the first intron of L-CPT I gene. Non-esterified fatty acids rather than acyl-CoA ester or intra-mitochondrial metabolite were responsible for the transcriptional effect on the gene encoding L-CPT I. It was shown that LCFA and peroxisome proliferators stimulated L-CPT I gene transcription by distinct mechanisms. Peroxisome proliferator stimulated L-CPT I gene transcription through a peroxisome-proliferator-responsive element (PPRE) located at -2846 bp, whereas LCFA induced L-CPT I gene transcription through a peroxisome-proliferator-activated receptor alpha (PPARalpha)-independent mechanism owing to a sequence located in the first intron of the gene.

Summaryaltered metabolism within maternal tissues may, in combination, Weight gain and food intake were measured in unstressed nonpregnant and pregnant guinea pigs fed ad libitum. Nonpregnant females consumed 33.2 k 0.5 goday-' of pellet diet and did not demonstrate a consistent pattern of weight gain. The average daily food intake of pregnant animals increased linearly from 38 g-day-' at 27 days to over 60 goday-' near term, and the average maternal weight gain was 13.3 goday-'.Using sterile technique, polyvinyl catheters were inserted under anesthesia into the carotid and femoral arteries of these animals. Animals recovered spontaneously, and catheters remained patent for up to 4 wk. The effect of surgical and anesthetic stress was evaluated by measurement of food intake and metabolite levels after surgery. In the nonpregnant animals, blood glucose decreased immediately after surgery (4.76 + 0.36 versus 5.65 f 0.25; P < 0.05), whereas the pregnant animals responded with a substantial increase in blood glucose (7.57 + 0.48 versus 5.87 + 0.33; P < 0.05). Lactate was increased intraoperatively in both groups (1.76 f 0.22 versus 1.11 + 0.07, nonpregnant; 1.80 + 0.17 versus 1.10 f 0.08, pregnant). The pregnant animals differed from the nonpregnant animals with regard to the pattern of changes in blood ketones after surgery. The nonpregnant animals achieved steady state within 1 day after surgery, whereas the pregnant animals required 4 days for recovery. Food intake and maternal weight gain were markedly reduced during the recovery period for the pregnant animals.Blood metabolite levels were measured in well-fed, unstressed pregnant and nonpregnant guinea pigs. Using measurements made after the third postoperative day, the unstressed pregnant animals demonstrated a progressive decline in blood glucose levels, reaching levels significantly below those of nonpregnant animals at 55 to 60 and 60+ days. Arterial concentrations of lactate, pyruvate, P-hydroxybutyrate, acetoacetate, and free fatty acids did not change consistently with gestation and were not significantly different from nonpregnant values. SpeculationIn animal studies, it is frequently difficult to differentiate the effects of advancing gestation from the effects of acute sample collection. Extension of these techniques of chronic catheterization to other areas of guinea pig metabolism and to other small mammalian species may provide more uniform conditions for the study of the comparative physiology of gestation and fetal development.The continuation of gestation may present a substantial challenge to the mother. Fetal oxidative and growth requirements, placental metabolic requirements, and requirements imposed by represent a signifi cant challenge to maternal nitrition and metabolism. The large variations among mammalian species both in fetal growth rate and in fetal body composition might be expected to produce a wide range in caloric requirements for fetal development. The guinea pig is particularly striking in producing a large fetal mass relative to...

resents the main site of control for the entry of LCFA into the mitochondria [Z] and mitochondrial Volume 23

The rates of glucose production from various substrates were investigated in isolated hepatocytes from fasting and suckling newborn pigs from birth to 48 hours of life. They were quantitatively compared to the rate of glucose production measured in 15-day-old suckling and fasting piglets. The data indicate that the rates of gluconeogenesis from each gluconeogenic precursor (lactate, pyruvate, alanine, glycerol, dihydroxyacetone and galactose) were two- to threefold higher in suckling than in fasting newborn pigs. The rates of glucose production from various gluconeogenic precursors were similar in suckling newborn pigs and in 15-day-old fasting piglets. The difference in the capacity for gluconeogenesis in isolated hepatocytes from fasting and suckling newborn pigs could explain why hypoglycemia develops during fasting in newborn pigs whereas suckling neonates remain normoglycemic.

In hepatocytes isolated from 48-hour-old suckling pigs, the inhibition of endogenous fatty acid oxidation leads to a 30% inhibition of glucose production from lactate. Addition of oleate plus carnitine to hepatocytes from 48-hour-old fasting pigs increases by 30% the rate of gluconeogenesis from lactate. In hepatocytes isolated from fasting newborn pigs, addition of glucagon (0.5 ng/ml) produces a 30% increase in the rate of glucose production from lactate and a 70% increase of glucose synthesis from dihydroxyacetone. The high rate of lactate plus pyruvate production in fasting piglets is markedly suppressed by glucagon and return to the value measured in suckling newborns. Combined addition of oleate and glucagon to hepatocytes from fasting piglets increases by 2-fold the rate of glucose production from lactate but does not restore totally the rate of glucose synthesis found in suckling piglets. It is concluded that fatty acid oxidation and hormonal environment contribute significantly to the development of an active gluconeogenesis in the newborn pig but do not represent the sole factors involved in the regulation of hepatic gluconeogenesis.

No abstract

No abstract

The inhibition of hepatic gluconeogenesis by 3-mercaptopicolinic acid (3-MPA) leads to a profound hypoglycemia in both suckling and fasting 24-hour-old rabbits. This hypoglycemia is totally reversed 1 h after the intragastric injection of an amount of galactose corresponding to the one ingested daily by the suckling newborns. This results from an active gluconeogenesis from galactose, which bypasses the site of inhibition by 3-MPA. However, this amount of galactose is not sufficient to maintain a normal blood glucose concentration for a long time, since 3 h after galactose injection, the blood glucose concentrations of newborn rabbits return to hypoglycemic values. When hepatic fatty acid oxidation is inhibited by 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (POCA), 24-hour-old fasting rabbits become rapidly hypoglycemic secondary to a decrease in liver gluconeogenesis. The rate of hepatic gluconeogenesis is totally restored by giving medium-chain triglycerides, and the 24-hour-old rabbits become normoglycemic.