Adipose Tissue Lipogenic Activities Research Articles

Influence of the diet and grazing on adipose tissue lipogenic activities and plasma leptin in steers

The objectives of the two experiments were to determine the respective effects and interactions of diet type (grass v. maize diets) and physical activity (grazing v. zero grazing) on lipogenic enzyme activities and adipose cell size in subcutaneous, perirenal and intermuscular adipose tissues and on plasma metabolites and hormones in Charolais steers. After weaning, the steers were assigned to two (Experiment 1, n = 24) or three (Experiment 2, n = 24) groups, with steers in Experiment 1 grazed grass or indoors maize-silage-fed and steers in Experiment 2 grazed grass, indoors cut grass- or indoors maize-silage-fed. Both experiments lasted for 23 months. All grass-fed animals were fed grass silage during the two winter seasons. During the two summer seasons, steers fed on grass were rotationally grazed on a perennial rye-grass pasture while steers fed on cut grass were fed indoors on freshly cut grass alone. Steers fed on maize silage were fed maize silage indoors during the entire experiment. All animals were reared for similar body weight and growth rates and slaughtered at the same age (31 to 32 months). Activities of lipogenic enzymes were significantly lower in the three adipose tissue sites of steers fed cut grass compared with maize silage, although there were less-marked effects in intermuscular adipose tissue. Plasma insulin and glucose concentrations were also lower in steers fed cut grass whereas plasma leptin concentration was similar. As body fat content was not affected by nutritional treatment, it is suggested that the decrease in potential lipogenic activity was associated with the nature of the diet and not to differences in available net energy. In other respects, grazed grass compared with eating cut grass did not affect lipogenic enzyme activities but decreased plasma leptin concentrations in the older steers and increased plasma non-esterified fatty acids and glucose concentrations without affecting adipose tissue weight and adipose cell size.

Effects of body condition score at parturition and postpartum supplemental fat on adipose tissue lipogenic activity of lactating beef cows1

Three-year-old Angus x Gelbvieh beef cows nutritionally managed to achieve a BCS of 4 +/- 0.07 (479.3 +/- 36.3 kg of initial BW) or 6 +/- 0.07 (579.6 +/- 53.1 kg of initial BW) at parturition were used in a 2-yr experiment (n = 36/yr) to determine the effects of BCS at parturition and postpartum lipid supplementation on cow adipose tissue lipogenesis. Beginning 3 d postpartum, cows within each BCS were randomly assigned to be fed hay and a low-fat control supplement or supplements with either cracked high-linoleate safflower seeds or cracked high-oleate safflower seeds until d 60 of lactation. Diets were formulated to be isonitrogenous and isocaloric, and safflower seed diets provided 5% DMI as fat. Adipose tissue biopsies were collected near the tail-head region of cows on d 30 and 60 of lactation. Dietary treatment did not affect (P > or = 0.43) adipose tissue lipogenesis. Body condition score at parturition did not affect acetate incorporation into lipid (P = 0.53) or activity of acetyl CoA carboxylase (P = 0.77) or fatty acid synthase (P = 0.18). Lipoprotein lipase activity and palmitate incorporation into triacyl-glycerol tended to be greater (P = 0.06), and palmitate esterification into total acylglycerols was greater (P = 0.01) in cows with a BCS of 4 at parturition. Mean activity of acetyl-CoA carboxylase (P < 0.001), lipoprotein lipase (P = 0.01), and rate of palmitate incorporation into monoacylglycerol (P = 0.02), diacylglycerol (P = 0.001), triacylglycerol (P = 0.003), and total acylglycerols (P = 0.002) were greater at d 30 than d 60, suggesting a greater proclivity for fatty acid biosynthesis and esterification by adipose tissue at d 30 of lactation. Although dietary lipid supplementation did not affect adipose tissue lipogenesis, results suggest that cows with a BCS of 4 at parturition have a greater propensity to deliver exogenously derived fatty acids to the adipocyte surface and incorporate preformed fatty acids into acylglycerols as stored adipocyte lipid. Additionally, cows in early lactation seemed to be able to synthesize and incorporate more fatty acids into stored lipid than cows during peak lactation.

Adaptation to a high protein, carbohydrate-free diet induces a marked reduction of fatty acid synthesis and lipogenic enzymes in rat adipose tissue that is rapidly reverted by a balanced diet

We have previously shown that in vivo lipogenesis is markedly reduced in liver, carcass, and in 4 different depots of adipose tissue of rats adapted to a high protein, carbohydrate-free (HP) diet. In the present work, we investigate the activity of enzymes involved in lipogenesis in the epididymal adipose tissue (EPI) of rats adapted to an HP diet before and 12 h after a balanced diet was introduced. Rats fed an HP diet for 15 days showed a 60% reduction of EPI fatty acid synthesis in vivo that was accompanied by 45%-55% decreases in the activities of pyruvate dehydrogenase complex, ATP-citrate lyase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and malic enzyme. Reversion to a balanced diet for 12 h resulted in a normalization of in vivo EPI lipogenesis, and in a restoration of acetyl-CoA carboxylase activity to levels that did not differ significantly from control values. The activities of ATP-citrate lyase and pyruvate dehydrogenase complex increased to about 75%-86% of control values, but the activities of glucose-6-phosphate dehydrogenase and malic enzyme remained unchanged 12 h after diet reversion. The data indicate that in rats, the adjustment of adipose tissue lipogenic activity is an important component of the metabolic adaptation to different nutritional conditions.

Regulation of leptin expression in farm animals

Leptin is a hormone mainly expressed by adipose tissue (AT) in mammals and/or by liver in birds, at levels that differ according to genetic, physiological, nutritional and environmental factors, as well as hormone treatments (Houseknecht et al., 1998; Barb et al., 2002; Chilliard et al., 2002; Taouis et al., 2002).AT leptin mRNA level was higher in sheep and goat subcutaneous than visceral tissues, and the opposite was observed in cattle; it was higher in fat than in lean selection line in sheep. Leptin gene expression was decreased by undernutrition and increased by refeeding in AT of cattle and sheep, and decreased during fasting but not after feed restriction in AT of pig. In the chicken, both AT and liver leptin mRNA were decreased by undernutrition. In lactating goats, the replacement of part of the dietary concentrates by soybeans did not change leptin expression. The injection of NPY in sheep, as well as growth hormone (GH) treatment of growing sheep and cattle increased AT leptin mRNA. In the pig, AT leptin mRNA decreased after GH administration and estrogen-induced leptin mRNA increased with age and adiposity. In the chicken, estrogen treatment decreased AT and liver leptin mRNA. In vitro, insulin and glucocorticoïds increased AT leptin mRNA in cattle and pig, and leptin production in sheep. However, these effects on leptin gene expression were inhibited by GH. In the chicken, liver but not AT leptin mRNA was either increased by insulin, glucocorticoïds and GH or decreased by glucagon treatments. Long daylength increased AT lipogenic activities and leptin mRNA, as well as plasma leptin in sheep. In sheep, AT leptin mRNA increased from prebreeding to mid-pregnancy and declined to prebreeding levels during early lactation (Ehrhardt et al., 2001).

Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration

This paper reviews data on leptin gene expression in adipose tissue (AT) and mammary gland of adult ruminants, as well as on plasma leptin variations, according to genetic, physiological, nutritional and environmental factors. AT leptin mRNA level was higher in sheep and goat subcutaneous than visceral tissues, and the opposite was observed in cattle; it was higher in fat than in lean selection line in sheep; it was decreased by undernutrition and increased by refeeding in cattle and sheep, and not changed by adding soybeans to the diet of lactating goats; it was increased by injection of NPY to sheep, and by GH treatment of growing sheep and cattle. Insulin and glucocorticoids in vitro increased AT leptin mRNA in cattle, and leptin production in sheep. Long daylength increased AT lipogenic activities and leptin mRNA, as well as plasma leptin in sheep. Mammary tissue leptin mRNA level was high during early pregnancy and was lower but still expressed during late pregnancy and lactation in sheep. Leptin was present in sheep mammary adipocytes, epithelial and myoepithelial cells during early pregnancy, late pregnancy and lactation, respectively. Plasma leptin in cattle and sheep was first studied thanks to a commercial “multi-species” kit. It was positively related to body fatness and energy balance or feeding level, and decreased by β-agonist injection. The recent development of specific RIA for ruminant leptin enabled more quantitative study of changes in plasma leptin concentration, which were explained for 35–50% by body fatness and for 15–20% by feeding level. The response of plasma leptin to meal intake was related positively to glycemia, and negatively to plasma 3-hydroxybutyrate. The putative physiological roles of changes in leptin gene expression are discussed in relation with published data on leptin receptors in several body tissues, and on in vivo or in vitro effects of leptin treatment.

Hormonal regulation of energy partitioning.

A loop system exists between hypothalamic neuropeptide Y (NPY) and peripheral adipose tissue leptin to maintain normal body homeostasis. When hypothalamic NPY levels are increased by fasting or by intracerebroventricular (i.c.v.) infusion, food intake and body weight increase. NPY has genuine hormono-metabolic effects. It increases insulin and corticosterone secretion relative to controls. These hormonal changes, acting singly or combined, favor adipose tissue lipogenic activity, while producing muscle insulin resistance. They also promote leptin release from adipose tissue. When infused i.c.v. to normal rats to mimic its central effects, leptin decreases NPY levels, thus food intake and body weight. Leptin i.c.v. has also genuine hormono-metabolic effects. It decreases insulinemia and adipose tissue storage ability, enhancing glucose disposal. Leptin increases the expression of uncoupling proteins (UCP-1, -2, -3) and thus energy dissipation. Leptin-induced changes favor oxidation at the expense of storage. Circadian fluctuations of NPY and leptin levels maintain normal body homeostasis. In animal obesity, defective hypothalamic leptin receptor activation prevent leptin from acting, with resulting obesity, insulin and leptin resistance.

The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats.

To determine the relative rates of glycogenesis and lipogenesis following administration of a test meal in lean and obese Zucker rats. Nine-week-old lean and obese Zucker rats were fasted overnight, then tube-fed a test meal of balanced composition amounting to 16kJ (lean rats and one group of obese rats) or 24kJ (one group of obese rats) and containing 200 mg 1-(13)C glucose. Immediately after the meal the rats were injected intraperitoneally with 5 mCi of 3H2O and killed 1 h later. Glycogenesis was calculated from the incorporation of 3H into liver glycogen divided by the specific activity of plasma water. Lipogenesis was calculated similarly from the incorporation of 3H into saponifiable lipids in liver and perirenal adipose tissue. The proportion of glycogen synthesized by the indirect pathway via pyruvate was determined from the ratio of 3H labelling at positions C6 and C2 in the glycogen glucose residues. Glycogen synthesis from glucose was determined from the ratio of 13C enrichment in liver glycogen to that in plasma glucose. The rate of synthesis of glycogen was considerably lower in the livers of obese rats than those of lean controls, with the larger meal causing a small but significant increase in glycogenesis. The proportion of glycogen synthesized via pyruvate showed a non-significant increase in the obese rats, while the amount of glycogen synthesized from glucose was significantly decreased. Hepatic lipogenic rates were about five times higher in both groups of obese rats than the lean controls. In adipose tissue, lipogenesis per g tissue was slightly reduced in the obese rats, although there was clearly an increase in adipose tissue lipogenic activity per whole animal. The larger meal caused a greater rise in plasma glucose and insulin concentrations but did not affect lipogenic rates, although it did cause a greater suppression of lipolysis, as indicated by a lower plasma glycerol concentration. Ingested carbohydrate is partitioned predominantly into hepatic fatty acid synthesis in obese Zucker rats. Hepatic glycogen synthesis is suppressed and comes mainly from precursors other than glucose. The suppression of hepatic glycogen synthesis may contribute to the increased energetic efficiency of obese Zucker rats.

Effects of photoperiod and feeding level on perirenal adipose tissue metabolic activity and leptin synthesis in the ovariectomized ewe.

Leptin is secreted by adipose tissue and plays a pivotal role in regulating both body energy homeostasis and reproductive function in rodents. Among livestock, sheep is a seasonal breeder whose reproductive period is initiated by short daylength. We show that plasma leptin and leptin gene expression in perirenal adipose tissue were decreased when ovariectomized Lacaune ewes were exposed to short days (8 versus 16 h light/d). This effect of the photoperiod occurred despite the nutritional status, with leptin levels lower in underfed than in refed ewes, and without significant changes in perirenal fat mass and adipocyte size. Plasma prolactin and leptin followed a similar pattern suggesting a relationship between the two hormones. These findings indicate, for the first time, that adipose tissue leptin is modulated by daylength independently of food intake, body fatness and gonadal activity. Furthermore, plasma non-esterified fatty acids of underfed ewes subjected to short days were more elevated than for underfed ewes on long days. On the other hand, refed ewes placed under long daylength tended to have a higher adipose tissue lipogenic activity than refed ewes on short days. We propose that these adaptations of leptin production and lipogenic activity with long photoperiod are of physiological significance for body fat deposition, which naturally occurs during long days when food is abundant. Conversely, a low leptin level during short days may enhance the sensitivity to food deprivation during the natural reproductive season, where any food shortage would decrease plasma leptin under a threshold critical for reproduction. Furthermore, in this situation, the observed enhanced ability to mobilize body fat may be related to the necessity to cope with energy shortage.

Central nervous system and peripheral abnormalities: clues to the understanding of obesity and NIDDM

To study the impact on glucose handling of the observed hyperinsulinaemia and hypercorticism of the genetically obese fa/fa rats, simplified animal models were used. In the first model, normal rats were exposed to hyperinsulinaemia for 4 days and compared to saline-infused controls. At the end of this experimental period, the acute effect of insulin was assessed during euglycaemic-hyperinsulinaemic clamps. White adipose tissue lipogenic activity was much more insulin responsive in the "insulinized" than in the control groups. Conversely muscles from "insulinized" rats became insulin resistant. Such divergent consequences of prior "insulinization" on white adipose tissue and muscle were corroborated by similar divergent changes in glucose transporter (GLUT 4) mRNA and protein levels in these respective tissues. In the second model, normal rats were exposed to stress levels of corticosterone for 2 days. This resulted in an insulin resistance of all muscle types that was due to an increased glucose-fatty acid cycle, without measurable alteration of the GLUT 4 system. In genetically obese (fa/fa) rats, local cerebral glucose utilization was decreased compared to lean controls. This could be the reason for adaptive changes leading to increased levels in their hypothalamic neuropeptide Y levels and median eminence corticotropin-releasing-factor. Thus, in a third model, neuropeptide Y was administered intracerebroventricularly to normal rats for 7 days. This produced hyperinsulinaemia, hypercorticosteronaemia, as well as most of the metabolic changes observed in the genetically obese fa/fa rats, including muscle insulin resistance. These data together suggest that the aetiology of obesity-insulin resistance of genetically obese rodents has to be searched within the brain, not peripherally.

Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity.

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 micrograms/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperphagia was prevented by pair-feeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under the ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose tissue; it resulted in an increase total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and metabolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperphagia was prevented by pair-feeding, it was, thus, shown that icv NPY per se induces peripheral hormonal and metabolic alterations via efferent routes, which remain to be determined. The effects of icv NPY reported in this study are similar to the defects observed in the early phase of genetic obesity in rodents, the hypothalamus of which has increased NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity.

Duodenal Rapeseed Oil Infusion in Early and Midlactation Cows. 5. Milk Fatty Acids and Adipose Tissue Lipogenic Activities

Lipogenic activities of perirenal adipose tissue were investigated in early (wk 3) and midlactation (wk 19 to 26) cows that received a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In midlactation, oil infusion resulted in a decreased rate of fatty acid synthesis from acetate and a decreased rate of the activities of fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas lipoprotein lipase activity tended to increase. The rate of glucose incorporation into glyceride-glycerol and the activities of glycerol-3-phosphate dehydrogenase and malic enzyme were not significantly affected. Fatty acid C14:0 content of perirenal adipose tissue was decreased, and fatty acid C18:2 and C18:3 contents were increased in oil-infused cows. In early lactation, rates of acetate incorporation into fatty acids and activities of fatty acid synthetase and lipoprotein lipase were very low. Activities of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase were lower in the early than in the midlactation trial. Oil infusion did not change the measured parameters. In both trials, percentages and yields of milk fatty acids C18:1, C18:2, and C18:3 were increased, whereas those of C14:0. and C16:0 were decreased by oil. Calculated transfer rates of absorbed fatty acid C18:2 from oil to milk fat were 16 to 26%. Results suggested that oil fatty acids affected adipose and mammary de novo lipogenesis in a direct way without affecting fatty acid esterification in adipose tissue or total fat secretion in mammary tissue.

Effect of swine weaning age on body fat and lipogenic activity in liver and adipose tissue.

Two experiments were conducted to evaluate the effects of weaning swine at 2 or 5 wk of age on postweaning performance and fat metabolism. In the first experiment, 52 pigs were weaned at 2 or 5 wk of age with body weights determined from birth to 8 wk. The early weaned group was fed a 20% protein corn-soybean meal-oat diet containing 25% dried whey from 2 to 5 wk while both groups were fed a 20% protein cereal grain-based diet from 5 to 8 wk of age. In a second experiment, a total of 90 pigs weaned at similar ages and fed the same diet sequences were killed at weekly intervals from 2 to 8 wk of age to evaluate body fat content and lipogenesis in liver and adipose tissue. Lipogenic capacity was measured by incorporation of acetate-1 14C into the total lipid fraction in liver slices and adipose tissue minces or by monitoring liver ATP citrate lyase activity. The results demonstrate that pigs weaned at 2 wk experience a slower postweaning growth rate with lower empty body weights than those either concurrently nursing the dam or weaned at 5 wk of age. Both groups had similar body weights from 6 to 8 wk of age. The body fat content of nursing pigs increased from 2 to 5 wk of age. Pigs weaned at 2 wk lost approximately 25% of their body fat the first week postweaning while later-weaned pigs did not lose body fat postweaning. Body fat composition of both groups was similar by 8 wk of age. Lipogenic activity was higher in liver than in adipose tissue from 2 to 5 wk of age and remained relatively constant throughout the trial. Adipose tissue lipogenic activity was lower in the nursing pig but increased dramatically at 5 wk in the early-weaned group and 7 wk of age in the late weaned group. These results suggest that weaning age can affect postweaning body fat composition and that adipose contributes a greater lipogenic capacity than liver tissue as the pig matures.

Dietary Carbohydrates in Hyperlipemia (Hyperglyceridemia); Hepatic and Adipose Tissue Lipogenic Activities

1. Controlled metabolic studies including periods of intersubstitution of sugar (mainly sucrose) and starch in the diet were made in a series of patients with carbohydrate-induced hyperglyceridemia. 2. Sugar feeding markedly exaggerated the hyperglyceridemia in all of the patients studied. Equicaloric substitution of starch for sugar in the diet resulted in lowering of the elevated serum lipids toward normal. 3. It was necessary to raise the daily carbohydrate intake to 85-90% of the total daily caloric intake in order to induce hyperglyceridemia in normolipemic subjects. 4. Hepatic and adipose tissues were obtained from normal subjects and hyperlipemic patients for lipogenesis and lipolytic activity studies. 5. The mean hepatic and adipose tissue lipogenic activities of hyperglyceridemic patients on relatively high carbohydrate ad libitum diet were found to be several times higher than those of normal controls on a similar diet. The tissue activities of patients maintained on sugar-restrictive carbohydrate moderation diet were normal. 6. The lipolytic activity of the hyperlipemic adipose tissue was many times more active than that of the normal controls and the diet-treated hyperglyceridemic patients. 7. Almost all radioactive 14C from the labeled precursors was incorporated into phospholipid by the liver tissues of both normal controls and lipemic patients. 8. The adipose tissue of normal controls incorporated the major proportion of the labeled precursors to water soluble fractions of the lipid molecule, and the adipose tissue of hyperglyceridemic patients incorporated 14C from isotopic acetate, fructose, and glucose predominantly into the fatty acid moiety of the newly synthesized lipid. 9. It is suggested that the adipose tissue of hyperglyceridemic patients on a high carbohydrate diet is highly active in lipid synthesis and also in the release of free fatty acids. The high fatty acid flux to the liver is esterified into triglyceride, incorporated into low density lipoproteins, and transported into the circulation with the aid of phospholipid to produce hyperglyceridemia. 10. Apparently healthy subjects with covert glyceride and carbohydrate metabolism are prone to the development of hyperglyceridemia when dietary sucrose content is increased. The association between dietary carbohydrate, hyperglyceridemia, and coronary artery disease is discussed.