Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal.

1. The effect of tumour burden on lipid metabolism was examined in virgin, lactating and litter-removed rats. 2. No differences in food intake or plasma insulin concentrations were observed between control animals and those bearing the Walker-256 carcinoma (3-5% of body wt.) in any group studied. 3. In virgin tumour-bearing animals, there was a significant increase in liver mass, blood glucose and lactate, and plasma triacylglycerol; the rate of oxidation of oral [14C]lipid to 14CO2 was diminished, and parametrial white adipose tissue accumulated less [14C]lipid compared with pair-fed controls. 4. These findings were accompanied by increased accumulation of lipid in plasma and decreased white-adipose-tissue lipoprotein lipase activity. 5. In lactating animals, tumour burden had little effect on the accompanying hyperphagia or on pup weight gain; tissue lipogenesis was unaffected, as was tissue [14C]lipid accumulation, plasma [triacylglycerol] and white-adipose-tissue and mammary-gland lipoprotein lipase activity. 6. On removal (24 h) of the litter, the presence of the tumour resulted in decreased rates of lipogenesis in the carcass, liver and white and brown adipose tissue, decreased [14C]lipid accumulation in white adipose tissue, but increased accumulation in plasma and liver, increased plasma [triacylglycerol] and decreased lipoprotein lipase activity in white adipose tissue. 7. The rate of triacylglycerol/fatty acid substrate cycling was significantly decreased in white adipose tissue of virgin and litter-removed rats bearing the tumour, but not in lactating animals. 8. These results demonstrate no functional impairment of lactation, despite the presence of tumour, and the relative resistance of the lactating mammary gland to the disturbance of lipid metabolism that occurs in white adipose tissue of non-lactating rats with tumour burden.     

Effects of hypergravity on mammary metabolic function: gravity acts as a continuum.

Mammary metabolic activity in pregnant rats is significantly increased in response to spaceflight. To determine whether changes in mammary metabolism are related to gravity load, we exposed pregnant rats to hypergravity and measured mammary metabolic activity. From days 11-20 of gestation (G), animals were centrifuged (20 rpm; 1.5, 1.75, or 2.0 x gravity) or were maintained at 1 G. On G20, five rats from each group were removed from the centrifuge and euthanized. The remaining dams (n = 5/treatment) were housed at 1 G until parturition. After 2 h of nursing by the pups, the postpartum dams were euthanized (G22). Glucose oxidation to CO2 and incorporation into lipids was measured. Mammary glands from dams euthanized on G20 revealed a strong negative correlation between metabolic rate and increased G load. Approximately 98% of the variation in glucose oxidation and 94% of the variation in glucose incorporation into lipids can be accounted for by differences in G load. Differences in metabolic activity disappeared in the postpartum dams. When we combined previous data from the microgravity with hypergravity environments and plotted the ratio of mammary metabolic rate vs. G load, there was a significant exponential relationship (r2 = 0.99). These data demonstrate a remarkable continuum of response across the microgravity and hypergravity environments and support the concept that gravitational load influences mammary tissue metabolism.     

Alterations in the activities of rat tissue hexose monophosphate dehydrogenases in response to premature weaning and dietary restriction at mid-lactation

Summary The activities of the hexose monophosphate dehydrogenases increased in adipose tissue, remained unchanged in liver and decreased in mammary gland following the weaning of rats at mid-lactation (day 14). When dietary intake was restricted at mid-lactation, the activities of the hexose monophosphate dehydrogenases increased in adipose tissue, decreased in liver, but were unaltered in mammary gland. Premature weaning on day 14 postpartum resulted in maternal increases in both plasma insulin and glucose, which peaked at day 16. The plasma insulin levels decreased from day 14 to day 18 postpartum in the normal lactating rat, and a similar trend was observed for animals on a restricted dietary intake. Daily food consumption in the lactating rat decreased from 50 g to 20 g after premature weaning. The live weight of pups raised on dams given a restricted food intake from day 14 had decreased by day 17 postpartum, whereas an increase in daily live weight gain was recorded for the litters from the lactating controls. The results demonstrate that the activities of the hexose monophosphate dehydrogenases are regulated differentially between tissues of the lactating rat.     

Characterization of MCH-mediated obesity in mice

Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus. Recently, we demonstrated that chronic intracerebroventricular infusion of MCH induced obesity accompanied by sustained hyperphagia in mice. Here, we analyzed the mechanism of MCH-induced obesity by comparing animals fed ad libitum with pair-fed and control animals. Chronic infusion of MCH significantly increased food intake, body weight, white adipose tissue (WAT) mass, and liver mass in ad libitum-fed mice on a moderately high-fat diet. In addition, a significant increase in lipogenic activity was observed in the WAT of the ad libitum-fed group. Although body weight gain was marginal in the pair-fed group, MCH infusion clearly enhanced the lipogenic activity in liver and WAT. Plasma leptin levels were also increased in the pair-fed group. Furthermore, MCH infusion significantly reduced rectal temperatures in the pair-fed group. In support of these findings, mRNA expression of uncoupling protein-1, acyl-CoA oxidase, and carnitine palmitoyltransferase I, which are key molecules involved in thermogenesis and fatty acid oxidation, were reduced in the brown adipose tissue (BAT) of the pair-fed group, suggesting that MCH infusion might reduce BAT functions. We conclude that the activation of MCH neuronal pathways stimulated adiposity, in part resulting from increased lipogenesis in liver and WAT and reduced energy expenditure in BAT. These findings confirm that modulation of energy homeostasis by MCH may play a critical role in the development of obesity.     

Expression of Human NSAID Activated Gene 1 in Mice Leads to Altered Mammary Gland Differentiation and Impaired Lactation

Transgenic mice expressing human non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) have less adipose tissue, improved insulin sensitivity, lower insulin levels and are resistant to dietary induced obesity. The hNAG-1 expressing mice are more metabolically active with a higher energy expenditure. This study investigates female reproduction in the hNAG-1 transgenic mice and finds the female mice are fertile but have reduced pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 expressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells on lactation day 2. Pups nursing from hNAG-1 expressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25 ng/mL) from hNAG-1 dams. The WT dams had no detectable hNAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development. To examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Microarray analysis revealed that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. Furthermore, the expression of Cidea/CIDEA that has been shown to regulate milk lipid secretion in the mammary gland was reduced in hNAG-1 mammary glands. This study suggests that expression of hNAG-1 in mice leads to impaired lactation and reduces pup survival due to altered milk quality and quantity.     

Effects of glucose-containing peritoneal-dialysis solutions on rates of lipogenesis in vivo in the liver, brown and white adipose tissue of chronic uraemic rats.

Chronic uraemic rats had decreased food intake, and this was accompanied by decreased weight of the epididymal fat-pads and interscapular brown adipose tissue. Normal rats whose food intake was restricted to an amount similar to that of the uraemic rats showed similar decreases in weight of the adipose-tissue depots. In addition, the food-restricted rats had decreased liver weight compared with normal or uraemic rats. The basal rate of lipogenesis was decreased in liver and epididymal fat-pads of food-restricted and uraemic rats and in interscapular brown adipose tissue of uraemic rats. Administration of a low-glucose-containing (1.36%) peritoneal-dialysis solution slightly increased lipogenesis in liver of uraemic rats, but had no significant effect in epididymal fat-pads. For brown fat, the rate of lipogenesis was increased in normal, food-restricted and uraemic groups, but the values for the last group were 4-5-fold lower than for the food-restricted or control groups. A high-glucose-containing (3.86%) peritoneal-dialysis solution gave similar rates of lipogenesis in liver, epididymal fat-pads and brown fat of all three groups, but for brown fat moderately uraemic rats showed a considerably lower rate of lipogenesis than did mildly uraemic rats. The basal plasma insulin concentration was lower in the food-restricted (50%) and uraemic (70%) groups than in the control group. The low-glucose peritoneal-dialysis solution increased plasma insulin to control values in the food-restricted rats, but had no significant effect on plasma insulin in the uraemic rats, despite a significant increase in blood glucose in this group. It is concluded that there is an impairment of the lipogenic response to intraperitoneal glucose loads in interscapular brown adipose tissue of uraemic rats, and that this is not due to the accompanying decrease in food intake. The hypoinsulinaemia may be an important factor. The possible relevance of this finding to the obesity observed in some uraemic patients treated by peritoneal dialysis with glucose-containing solutions is discussed.     

De novo lipogenesis and lipolysis activities in normal (Dw) and dwarf (dw) White Leghorn laying hens

1. In vitro activities of glucose oxidation, de novo lipogenesis and lipolysis were compared in normal (Dw) and dwarf (dw) laying hens. 2. Dwarfism reduced the hepatic glucose oxidation while de novo lipogenesis was not altered. As liver weight was depressed, total liver lipogenesis capacity was probably reduced by dwarfism. 3. As compared to normal hens, de novo lipogenesis and basal or stimulated lipolysis were lower in dwarf adipose tissue while its lipid content was enhanced in dwarfs. 4. Results suggest that in laying hens dwarfism reduces the adipose tissue lipid mobilization but probably also the liver de novo lipogenesis.     

In vivo lipogenesis and enzyme levels in adipose and liver tissues from pair-fed genetically obese and lean rats

Genetically obese Zucker rats pair-fed to lean controls were similar in body weight and food intake, however, epididymal fat pads were considerably larger than lean controls. $\text{In}$$\text{vivo}$ incorporation of acetate-¹⁴C into adipose tissue lipid was not significantly different, however, $\text{in}$$\text{vivo}$ liver lipogenesis was elevated in the obese rat. Characterization of enzyme profiles in both liver and adipose tissues revealed that enzymes normally associated with lipogenesis were elevated in liver tissue from obese rats. Malic enzyme and citrate cleavage enzyme were both depressed in adipose tissue of obese animals. From these data, it appears that the liver may be prominently involved in the development of excessive blood lipid and enlarged fat cells in the Zucker obese rat.     

The Dietary Protein/Carbohydrate Ratio Differentially Modifies Lipogenesis and Protein Synthesis in the Mammary Gland,Liver and Adipose Tissue during Gestation and Lactation

During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.     

Epidermal growth factor and parathyroid hormone-related peptide mRNA in the mammary gland and their concentrations in milk: effects of postpartum hypoxia in lactating rats.

The physiological adaptations of the neonatal rat to hypoxia from birth include changes in gastrointestinal function and intermediary metabolism. We hypothesized that the hypoxic lactating dam would exhibit alterations in mammary gland function leading to changes in the concentration of milk peptides that are important in neonatal gastrointestinal development. The present study assessed the effects of chronic hypoxia on peptides produced by the mammary glands and present in milk. Chronic hypoxia decreased the concentration of epidermal growth factor (EGF) in expressed milk and pup stomach contents and decreased maternal mammary gland EGF mRNA. The concentration of parathyroid hormone-related protein (PTHrp) was unchanged in milk and decreased in pup stomach contents; however, mammary PTHLH mRNA was increased by hypoxia. There was a significant increase in adiponectin concentrations in milk from hypoxic dams. Chronic hypoxia decreased maternal body weight, and pair feeding normoxic dams an amount of food equivalent to hypoxic dam food intake decreased body weight to an equivalent degree. Decreased food intake did not affect the expression of EGF, PTHLH, or LEP mRNA in mammary tissue. The results indicated that chronic hypoxia modulated mammary function independently of hypoxia-induced decreases in maternal food intake. Decreased EGF and increased adiponectin concentrations in milk from hypoxic dams likely affect the development of neonatal intestinal function.     

Effect of weaning time on the growth rate and food intake of the spiny mouse pup

The spiny mouse Acomys cahirinus produces well-developed pups although it is a relatively small mammal (45 g). We envisioned two opposing hypotheses on the effect of early weaning on the growth rate of pups. The first predicts little effect since the increase in energy intake of dams above non-reproducing females is relatively low, suggesting that pups consume a large portion of their energy as solid food, and the pups are very well developed at birth. The second predicts a substantial effect since the 'index of precociality', that is the energy intake for maintenance of a pup as a proportion of that predicted for a rodent of its body mass, falls within values for altricial rodents, suggesting an extended maternal dependence of the young. To test these hypotheses, we measured the growth rate and food intake of pups weaned after either 7, 14, 21 or 28 days. Only three of 12 pups weaned after 7 days survived and, consequently, the latter hypothesis was supported. All pups weaned at 14–28 days survived. There was a significant decrease in growth rate during the first day after weaning in pups weaned at 7, 14 and 21 days but not after 28 days, suggesting that pups did not require parental care by day 28. Peak growth rate in pups weaned at 14 days occurred in the second week but occurred in the third week in pups weaned at 21 and 28 days. In spite of these differences, pups in all treatments had similar body mass at 64 days, indicating compensatory growth. We concluded that pups of A. cahirinus are precocial from a morphological aspect in that they are well developed at birth but altricial from a nutritional aspect in that they require extended maternal support.     

Tissue-specific effects of starvation and refeeding on the disposal of oral [1-14C]triolein in the rat during lactation and on removal of litter.

1. The effects of starvation and refeeding on the disposal of oral [14C]triolein between 14CO2 production and 14C-lipid accumulation in tissues of virgin rats, lactating rats and lactating rats with pups removed were studied. 2. Starvation (24 h) increased 14CO2 production in lactating rats and lactating rats with pups removed to values found in virgin rats. This increase was accompanied by decreases in 14C-lipid accumulation in mammary gland and pups of lactating rats and in white and brown adipose tissue of lactating rats with pups removed. 3. Short-term (2 h) refeeding ad libitum decreased 14CO2 production in lactating rats and lactating rats with pups removed, and restored the 14C-lipid accumulation in mammary glands plus pups and in white and brown adipose tissue respectively 4. Insulin deficiency induced with mannoheptulose inhibited the restoration of 14C-lipid accumulation in white adipose tissue on refeeding of lactating rats with pups removed, but did not prevent the restoration of 14C-lipid accumulation in mammary gland. 5. Changes in the activity of lipoprotein lipase in mammary gland and white adipose tissue paralleled the changes in 14C-lipid accumulation in these tissues. 6. It is concluded that 14C-lipid accumulation in mammary gland may not be affected by changes in plasma insulin concentration and that it is less sensitive to starvation than is lipogenesis or lactose synthesis. This has the advantage that the milk lipid content can still be maintained from hepatic very-low-density lipoprotein for a period after withdrawal of food. The major determinant of the disposal of oral 14C-triolein appears to be the total tissue activity of lipoprotein lipase. When this is high in mammary gland (fed lactating rats) or white adipose tissue (fed lactating rats with pups removed), less triacylglycerol is available for the muscle mass and consequently less is oxidized.     

Hepatic insulin binding following in utero exposure to ethanol

Insulin binding to liver membranes has been studied in term fetuses of rats fed ethanol-containing liquid diet during pregnancy . Pair-fed and ad libitum-fed controls received liquid diet in which maltose-dextrins were substituted isocalorically for ethanol. Food consumption and body weigh gain of ethanol- imbibing dams were 35% and 70% less than their ad libitum counterparts respectively. Ethanol-fed rats also exhibited less gain in body weight than pair-fed controls despite isocalorically equivalent food intake. The number of live pups was not different among the various groups; however, liver weight of fetuses exposed to ethanol in utero was 47% less than those of the pups of ad libitum control dams and 28% less than those of the offspring of pair-fed control rats. Insulin binding to liver membranes of fetuses exposed to ethanol in utero was lower than that of ad libitum controls but was not significantly different from that of the pair-fed control animals. Average affinity profiles showed a reduction in K at all levels of receptor occupancy in the fetuses of ethanol-fed rats. For fetuses of the pair-fed group, K was reduced only at fractional occupancy below 20% but not at higher fractional occupancy. Because of the similarity of insulin binding in the fetuses of the ethanol-fed rats and their pair-fed counterparts, effects of ethanol on insulin binding cannot account for the reduced hepatic glycogen stores previously reported in term fetuses.     

Effect of thyroidectomy on pathways of glucose metabolism in lactating rat mammary gland

1. Assessment of the overall metabolic changes in lactating mammary gland after thyroidectomy has been made by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into (14)CO(2) and (14)C-labelled lipid in the experimental rats and in sham-operated control animals. 2. Thyroidectomy depressed the oxidation of (14)C-labelled substrates, an effect still apparent when the control rats were pair-fed with thyroidectomized rats; however, the ratio of oxidation of [1-(14)C]glucose/oxidation of [6-(14)C]glucose was unaltered. In parallel with these studies it was revealed that the activities of hexokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-linked isocitrate dehydrogenase were all lower in the thyroidectomized group than in the pair-fed control group. 3. Thyroidectomy also lowered the incorporation of (14)C-labelled substrates into (14)C-labelled lipid, an effect further studied by measurement of the activities of citrate-cleavage enzyme and acetate thiokinase. Restricting the food intake of the control rats to that of the thyroidectomized group lowered the activity of citrate-cleavage enzyme, but no further depression was observed on thyroidectomy. The oxidized and reduced nicotinamide nucleotide content of mammary tissue was shown to be decreased in the thyroidectomized rats compared with the control rats.     

Different effects on zinc redistribution if ethanol is consumed before or immediately after birth

AimsThe effect of ethanol consumption, either during pregnancy and/or lactation, on the altered metabolism of zinc (Zn) is not well-defined. Therefore, this study was performed to analyse the effect of chronic ethanol exposure on Zn redistribution in dams and offspring during either gestation and/or lactation.MethodsWe have used three groups of Wistar rat dams: control (CD), ethanol (ED), and pair-fed dams (PD). Some of the newborns were cross-fostered to dams at birth and we formed five experimental groups of offspring: control (CO); those exposed to ethanol during gestation only (GO); those exposed to ethanol during lactation only (LO); those exposed to ethanol during both periods (EO); and pair-fed groups (PO). Zn levels were measured by flame atomic absorption spectrophotometry.ResultsZinc distribution is altered in ED with respect to CD, presenting significantly higher Zn values in the brain and spleen, and lower levels in the liver. However, total organs Zn levels are similar between dams. Ethanol-treated offspring (GO, LO, EO) consumed significantly less Zn than the CO. However, LO and EO showed significantly higher Zn serum levels. Zn distribution was altered in ethanol-treated offspring. GO and LO showed lower Zn levels in liver than CO; GO presents the lowest Zn liver levels. These levels were significantly lower than EO and PO. Ethanol-treated pups present significantly higher spleen and testes values than CO and PO. Total organ Zn levels were significantly lower in GO.ConclusionsMaternal adaptation resulted in organ Zn retention in order to meet the demands of pup’s growth in the face of a lower diet intake. However, there was a redistribution of Zn in organ contents. Therefore, the ethanol route administration (via placenta and/or milk) affects Zn redistribution in pups in a different way.     

3,5,3'-Triiodothyronine administered to rat dams during lactation increases milk yield and triglyceride concentration and hastens pups growth

It is known that lactation induces a mild hypothyroid state in rats and other mammals while thyroid hormone administration increases milk secretion in ruminants. The aim of this study was to investigate the effects of a moderate dose of 3,5,3'-triiodothyronine (T3), administered to rat dams during lactation on pups' growth and milk yield and composition. Primiparous Wistar rats with litters adjusted to 10 pups per dam received either tap water or T3 (75 microg/kg x day) in their drinking water from parturition till weaning. Food and water intake of dams and body weight of dams and pups were measured daily. In other groups of rats with similar treatments, milk yield of dams, macronutrient milk composition, and mammary arteriovenous differences for triglycerides (TG) and glucose were also determined. Dams treated with T3 ingested more food and their pups gained more weight than controls. Milk yield, milk TG concentration and glucose extraction by mammary glands were also higher in T3 treated dams. The results show that compensation of the mild hypothyroidism of the lactating rat may contribute to an increase in milk production and lipid levels, leading to an increase in growth of pups.     

The administration of oleoyl-estrone to lactating dams induces selective changes in the normal growth pattern of their pups.

To determine the effects of oleoyl-estrone treatment on the lactating dams and on the growth pattern of developing rats, female Wistar rats were randomly divided into two groups after delivery. One group received a daily gavage of 0.2 mL sunflower oil containing 10 micromol oleoyl-estrone/kg (treated group) and the other received a daily intragastric gavage of 0.2 mL sunflower oil (control group). Treatment was carried out during the first 15 days of lactation. Dams were killed on days 1, 15 or 20 after delivery and pups were sacrificed on days 1, 15, 20 or 30. Treated dams showed a transient decrease in food intake, significant lower lipid content than control dams, with a parallel maintenance of protein content and no appreciative changes in plasmatic parameters. However, a significant increase in brown adipose tissue mass was detected in treated group. Pups from treated dams showed a decrease in their growth rate that was reflected in the lower adipose tissue mass in different locations, except in the case of brown adipose tissue and, that continued after cessation of treatment. Thus, treatment affects dams in a selective way that does not coincide with a simple food restriction model.     

Influence of early nutrition on growth and adipose tissue characteristics in male and female rats

The purpose of this investigation was to assess the effects of early nutrition on adipose tissue characteristics and growth by altering litter size. After birth, rats were redistributed into large (15-18 pups), control (10 pups), or small (4 pups) litters. During the postweaning phase of growth half of the small-litter animals were pair-fed to animals raised in large litters for 5 wk and then allowed to feed ad libitum until they were 80 days of age. The small-litter males gained weight at a more rapid rate than the other litter types, both before and after weaning, and attained a final body weight twofold greater than the other groups. The small-litter males had significantly higher (P less than 0.05) numbers of adipocytes per epididymal fat pad than the other litter groups with 60.4, 51.4, and 79.0% greater cell number per pad than control, large, and pair-fed animals, respectively. Limiting food intake to small-litter animals after weaning (pair-fed) inhibited this growth and prevented fat cell proliferation. Litter manipulation had significant effects on male rats, but the same treatment did not influence female rats. Litter size influenced fat cell characteristics but had little effect on the adipocytes' ability to take up or metabolize glucose. The major finding, in terms of insulin responsiveness, was the difference between the sexes. The uptake of tritiated 2-deoxyglucose by the fat cells of female litter groups was significantly higher than that of the males whether insulin was present or not, whereas the conversion of [1-14C]glucose to CO2 by the adipocytes of females was lower than that of the males.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of lactating-rat mammary-gland lipogenesis by insulin and glucagon in vivo. The role and site of action of insulin in the transition to the starved state.

Starvation for 6h and 24h caused an 80% and 95% decrease in the rate of mammary-gland lipogenesis respectively in conscious lactating rats. 2. Plasma insulin concentrations decreased and circulating ketone-body concentrations increased with the length of starvation. 3. The inhibition of lipogenesis after 24h starvation was accompanied by increased concentrations of glucose, glucose 6-phosphate and citrate in the mammary gland. Qualitatively similar changes were observed after 6h starvation. 4. Infusion of insulin at physiological concentrations caused a 100% increase in the rate of lipogenesis in fed animals and partially reversed the inhibition of lipogenesis caused by starvation. 5. Infusion of insulin tended to reverse the changes seen in intracellular metabolite concentrations. 4. Infusion of glucagon into fed rats caused no change in the rates of lipogenesis in mammary gland, liver or white adipose tissue. 7. It is concluded that (a) insulin acts physiologically to regulate lipogenesis in the mammary gland, (b) hexokinase and phosphofructokinase are important regulatory enzymes in the short-term control of lipogenesis in the mammary gland, which are under the influence of insulin, and (c) the unresponsiveness of mammary-gland lipogenesis in vivo to infusions of glucagon is consistent with an adaptive mechanism which diverts substrate towards the lactating mammary gland and away from other tissues.