Regulation Of Adipose Tissue Metabolism Research Articles

RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27

Adipose tissue modulates whole body metabolism and insulin sensitivity by controlling circulating lipid levels and producing molecules that can regulate fatty acid metabolism in such tissues as muscle and liver. We have developed RNA interference (RNAi) screens to identify genes in cultured adipocytes that regulate insulin signalling and key metabolic pathways. These short interfering RNA (siRNA)-based screens identified the transcriptional corepressor receptor interacting protein 140 (RIP140) (J Clin Invest 116: 125, 2006) and the mitogen-activated protein kinase (MAP4k4) (Proc Natl Acad Sci USA 103: 2087, 2006) as negative regulators of insulin-responsive hexose uptake and oxidative metabolism. Gene expression profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, tricarboxylic acid cycle, fatty acid oxidation, mitochondrial biogenesis and oxidative phosphorylation. RIP140-null mice resist weight gain on a high-fat diet and display enhanced glucose tolerance. MAP4k4 depletion in adipocytes increases many of the RIP140-sensitive genes, increases adipogenesis and mediates some actions of tumour necrosis factor-alpha (TNF-alpha). Remarkably, another hit in our RNAi screens was fat specific protein 27 (FSP27), a highly expressed isoform of Cidea. We discovered that FSP27 unexpectedly associates specifically with lipid droplets and regulates fat storage. We conclude that RIP140, MAP4k4 and the novel lipid droplet protein FSP27 are powerful regulators of adipose tissue metabolism and are potential therapeutic targets for controlling metabolic disease. The discovery of these novel proteins validates the power of RNAi screening for discovery of new therapeutic approaches to type 2 diabetes and obesity.

Variations in parametrial white adipose tissue mass during the mouse estrous cycle: relationship with the expression of peroxisome proliferator-activated receptor-γ and retinoic acid receptor-α

Estrogen and progestin participate in the regulation of adipose tissue metabolism, and peroxisome proliferator-activated receptor-gamma (PPARgamma) and retinoic acid receptor-alpha (RXRalpha) are absolutely required for adipose tissue development. The present study is to investigate the changes in parametrial fat mass and expression of PPARgamma and RXRalpha during estrous cycle in mice. Parametrial white adipose tissues (WAT), inter-scapula brown adipose tissues, and uteri from female mice were weighed. Blood samples were collected for the measurement of 17 beta-estradiol and progesterone levels. An RNase protection assay and Western blot analysis were used to compare the expression of PPARgamma and RXRalpha in adipose tissue. The mass of parametrial WAT in diestrus was significantly higher compared with estrus. However, there is no significant difference on the mass of brown adipose tissues during estrous cycle. The expression of PPARgamma in WAT in diestrus was significantly higher than that in estrus. The expression of RXRalpha during estrous cycle was unchanged in both white and brown adipose tissues. In conclusion, the variation in parametrial WAT mass during the mouse estrous cycle correlates with changes in the expression of PPARgamma in WAT.

Dihydrotestosterone Treatment Results in Obesity and Altered Lipid Metabolism in Orchidectomized Mice

To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.

INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE POLYMORPHISM AND TRADITIONAL CLASSIFICATION IN OBESE WOMEN

Cytokines appear to be the major regulators of adipose tissue metabolism. Interleukin- 1 receptor antagonist (IL-1ra) serum levels are increased in human obesity, and are under strong genetic control. The hypothesis was tested that the IL-1ra gene might be a candidate for obesity. Furthermore, the relationship was investigated between Sasang constitution and IL-1ra polymorphism. The frequency of a penta-allelic 86-bp tandem repeat (VNTR) in the intron 2 of IL-1ra gene in 67 lean (BMI < 25 kg/m2), 133 overweight (BMI 25-29.9 kg/m2) and 61 obese (BMI ≥ 30 kg/m2) otherwise healthy Korean subjects was investigated. Total fat mass and percentage body fat were determined by dual-energy X-ray absorptiometry. Subjects were discriminated into four types by QSCC II program as well as clinical data (weight, height, blood pressure, etc.); Teaeumin, Taeyangin, Soyangin, and Soeumin. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of IL-1ra. The genotypic, or allelic distribution did not differ markedly between the three groups. The relative risk of being obese in comparison with lean was twofold increased in allele 2 carriers, although it was not statistically significant. Carriers of the allele 2 did not show a significant difference in physical and clinical characteristics. However, the relative risk of being obese in comparison with lean was increased in Taeumin subjects (p = .050), and so was in IL-1ra A2- carriers (p = .047). No relationship was found between the IL-1ra polymorphism and BMI in Korean women, but the authors first attempted to find an association among IL-1ra polymorphism, obesity, and Sasang constitution.

Transgenic animal models for the study of adipose tissue biology

The traditional view of adipose tissue as a passive energy reservoir has changed. Adipose tissue is a complex, highly active metabolic and endocrine organ. With obesity as an increasingly important public health threat, a major development in the understanding of adipose tissue biology has come with observations in different biological spheres including whole-body physiology and application of transgenic animal models. Scientific progress has been made with the identification of several genes in spontaneous monogenic animal models of obesity, and in understanding the molecular mechanisms underlying phenotypes of altered body weight, adiposity and fat distribution by creating transgenic and knockout animal models. Mouse phenotypes resulting from inactivation or overexpression of molecules responsible for the regulation of adipose tissue metabolism have led to novel concepts in the understanding of adipocyte biology and development of obesity. This review presents an overview of transgenic animal models for the study of adipose tissue biology.

Polymorphism of interleukin-1 receptor antagonist gene and obesity

Background: Cytokines appear to be major regulators of adipose tissue metabolism. Interleukin-1 receptor antagonist (IL-1ra) serum concentrations are increased in human obesity, and are under strong genetic control. We tested the hypothesis that the IL-1ra gene might be a candidate for obesity. Methods: We investigated the frequency of a penta-allelic 86-bp tandem repeat (VNTR) in the intron 2 of IL-1ra gene in 52 lean (body mass index (BMI) <25 kg/m 2), 133 overweight (BMI 25–29.9 kg/m 2) and 76 obese (BMI ≥30.0 kg/m 2) otherwise healthy Korean women. Total fat mass and percent body fat were determined by dual-energy X-ray absorptiometry. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of IL-1ra. Results: Carriers of the allele 2 did not show a significant difference in physical and clinical characteristics. The genotypic, or allelic distribution did not differ markedly between the three groups. The relative risk of being obese in comparison with lean group tended to be higher in allele 2 carriers, but not significantly. Conclusions: We found no relationship between the IL-1ra polymorphism and BMI in Korean women.

Evaluation of serum leptin levels and thyroid function in morbidly obese patients treated with bariatric surgery.

Biliopancreatic diversion (BPD), a gastrectomy with a long ROUX en Y reconstruction, reduces intestinal absorption by delaying the mixing of food and biliopancreatic juices, and induces persistent weight loss in obese patients unresponsive to medical treatments. The levels of leptin (a plasma protein synthesised in human adipose tissue) are increased in obese subjects and significantly decrease after a major weight loss. A possible role of thyroid hormones in regulating adipose tissue metabolism in humans has been proposed, but it is not universally accepted and the relationship between thyroid function and leptin levels has not yet been clearly defined. We studied serum leptin, TSH, fT4 and fT3 levels in 38 obese patients (26 women and 12 men), before and 12 months after BPD. There was a significant post-surgical decrease in BMI and circulating leptin levels in all of the treated subjects, but thyroid function did not seem to be affected (TSH and fT4 levels were unchanged). However, fT3 levels significantly decreased after surgery. Our data suggest that BPD-induced malabsorption has no direct effect on thyroid function, but possibly reduces the peripheral conversion of thyroxine to T3. Further studies seem to be necessary to clarify the clinical relevance of these observations.

Nutritional regulation of lipid metabolism in human adipose tissue.

Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.

Pro-inflammatory cytokines and adipose tissue.

Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor alpha (TNF-alpha) and several interleukins (IL), notably IL-1beta and IL-6. Other adipocyte products with 'immunological' actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-alpha and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-alpha mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual 'inflammatory' stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-alpha. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-alpha and IL-6 inhibit lipoprotein lipase, and TNF-alpha additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-alpha also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more 'trophic', and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor gamma). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of beta3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-alpha is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-alpha is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.

Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats.

We have previously reported that attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, increased insulin sensitivity and reduced body weight in obese Zucker rats. These findings prompted us to investigate the effects of DZ on key insulin-sensitive enzymes regulating adipose tissue metabolism, fatty acid synthase (FAS), and lipoprotein lipase (LPL), as well as on circulating levels of leptin. We also determined the direct effects of diazoxide on FAS in 3T3-L1 adipocytes. Seven-week-old female obese and lean Zucker rats were treated with DZ (150 mg/kg/d) or vehicle (C, control) for a period of 6 wk. Changes in plasma parameters by DZ include significant decreases in triglycerides, free fatty acids, glucose, and insulin, consistent with our previous reports. DZ obese rats exhibited lower plasma leptin levels (P<0.03) compared to their C animals. DZ significantly reduced adipose tissue FAS activity in both lean (P<0.0001) and obese (P<0.01) animals. LPL mRNA content was also decreased significantly in DZ-treated obese animals (P<0.009) as compared to their respective controls without a significant effect on lean animals. The possibility that DZ exerted a direct effect on adipocytes was further tested in cultured 3T3-L1 adipocytes. Although diazoxide (5 microM) alone did not change FAS activity in cultured 3T3-L1 adipocytes, it significantly attenuated insulin's effect on FAS activity (P<0.001). We demonstrate that DZ regulates key insulin-sensitive enzymes involved in regulation of adipose tissue metabolism. These findings suggest that modification of insulin-sensitive pathways can be therapeutically beneficial in obesity management.

Cellular adaptations in fat tissue of exercise-trained miniature swine: role of excess energy intake

This study examined the influence of energy expenditure and energy intake on cellular mechanisms regulating adipose tissue metabolism. Twenty-four swine were assigned to restricted-fed sedentary, restricted-fed exercise-trained, full-fed sedentary, or full-fed exercise-trained groups. After 3 mo of treatment, adipocytes were isolated and adipocyte size, adenosine A(1) receptor characteristics, and lipolytic sensitivity were measured. Swine were infused with epinephrine during which adipose tissue extracellular adenosine, plasma fatty acids, and plasma glycerol were measured. Results revealed that adipocytes isolated from restricted-fed exercised swine had a smaller diameter, a lower number of A(1) receptors, and a greater sensitivity to lipolytic stimulation, compared with adipocytes from full-fed exercised swine. Extracellular adenosine levels were transiently increased on infusion of epinephrine in adipose tissue of restricted-fed exercised but not full-fed exercised swine. These results suggest a role for adenosine in explaining the discrepancy between in vitro and in vivo lipolysis findings and underscore the notion that excess energy intake dampens the lipolytic sensitivity of adipocytes to beta-agonists and adenosine, even if accompanied by exercise training.

Tumor necrosis factor-alpha-induced insulin resistance in adipocytes.

Recent studies examining the link between insulin resistance and the development of obesity and noninsulin-dependent diabetes mellitus are consistent with the involvement of tumor necrosis factor-alpha (TNF-alpha) as a central mediator. In insulin resistant obese mouse models, neutralization of TNF-alpha in circulation has been demonstrated to restore insulin-mediated glucose uptake. Adipose tissue has been shown to be a site for synthesis of TNF-alpha, with the degree of adiposity directly correlated with the level of synthesis. Studies conducted on obese human patients have demonstrated a correlation between levels of TNF-alpha, the extent of obesity, as well as the level of hyperinsulinemia observed. Mechanistic studies in cell culture have suggested that TNF-alpha functions to render cells insulin resistant through regulation of the synthesis of the insulin responsive glucose transporter as well as through interference with insulin signaling. This review will address these issues and additionally introduce the reader to the molecular aspects of TNF-alpha, its receptors as well as TNF-alpha-initiated signaling cascades, that are necessary to understand the function of this cytokine in the regulation of adipose tissue metabolism.

Somatotropin Regulates Adipose Tissue Metabolism in Neonatal Swine

Somatotropin (ST) reduces lipid deposition in growing and adult animals, but its effect in neonatal pigs is not clear. In this study, we tested the hypothesis that ST inhibits lipid deposition in neonatal pig adipose tissue. Four neonatal (2.9 ± 0.1 kg, 7 d of age) and four growing (17.0 ± 1.4 kg, 60 ± 3 d of age) crossbred pigs were used. Subscapular adipose tissue fragments were cultured with or without ST (4.5 nmol/L) for 24 h in the absence or presence of insulin (7 nmol/L). After culture for 24 h with insulin alone, adipocytes from neonatal and growing pig adipose tissue maintained the capacity to incorporate glucose into total lipid at rates comparable to those in fresh tissue. Culture for 24 h with ST in the presence or absence of insulin decreased adipocyte glucose incorporation into fatty acids. Addition of ST, in the absence or presence of insulin, also increased the accumulation of glycerol in the medium during culture of neonatal and growing pig adipose tissue. Furthermore, culture for 24 h with ST resulted in higher basal lipolysis measured during incubation of isolated adipocytes in the presence of adenosine deaminase. In addition, culture with ST decreased adipose tissue lipoprotein lipase (LPL) activity and completely blocked the stimulatory effect of insulin on activity of this enzyme. The present study is the first to demonstrate in neonatal pigs that, as in growing pigs, ST regulates adipose tissue metabolism through decreasing lipid synthesis and LPL activity and increasing lipolysis. Thus, ST may play an important role in nutrient partitioning during the neonatal period.

Effect of Overfeeding During the Dry Period on Regulation of Adipose Tissue Metabolism in Dairy Cows During the Periparturient Period

During the dry period, cows were either fed restricted amounts or were overfed to study lipolytic rates in adipose tissue. Higher lipolytic rates can result in greater accumulation of triacylglycerols in liver and, subsequently, hepatic lipidosis. Adipose tissue was biopsied at –1, 0.5, 1, 2, and 3 wk from parturition. The basal in vitro lipolytic rate was measured as well as the lipolytic rate as affected by the addition of noradrenaline, 3-hydroxybutyrate, or glucose. Liver was biopsied to quantify triacylglycerol concentrations. Blood was collected to determine insulin and nonesterified fatty acid concentrations. Basal in vitro lipolytic rates at –1 and 0.5 wk were lower in overfed cows. Lipolytic rate was enhanced in both groups of cows when noradrenaline was added, but rates at –1 and 3 wk tended to be higher in overfed cows than in cows that were fed restricted amounts. After the addition of 3-hydroxybutyrate or glucose in vitro, lipolytic rates tended to be higher in overfed cows. Liver triacylglycerol concentration was higher in overfed cows at 0.5 and 1 wk. Plasma insulin concentration tended to be higher in overfed cows at –1 wk. Plasma nonesterified fatty acid concentration was higher in overfed cows at 0.5 and 1 wk. Although overfeeding compared with restricted feeding did not significantly alter the in vitro lipolytic response to 3-hydroxybutyrate or glucose, adipose tissue from overfed cows tended to be less inhibited by these substances, which may contribute to higher lipolytic rates in vivo and a greater triacylglycerol accumulation in the liver after parturition.

Hormonal control of regional fat distribution.

Hormones exert powerful influences on body fat distribution in humans. Studies under fully controlled conditions in vitro have indicated that cortisol and insulin facilitate lipid accumulation by expressing lipoprotein lipase (LPL). Growth hormone (GH) abolishes this and turns metabolism towards lipid mobilization. Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Cortisol effects are mediated via a glucocorticoid receptor, and testosterone effects via an androgen receptor, the density of which appears to be higher in visceral than subcutaneous adipose tissue. The receptor-mediated effects are probably expressed via transcription of appropriate genes. The female sex steroids also regulate adipose tissue metabolism, but apparently not directly in the absence of specific cellular receptors. Oestrogens seem to exert net effects similar to those of testosterone. These results of cellular studies agree well with in-vivo studies of triglyceride uptake and turnover in different adipose tissue regions. Furthermore, clinical entities with characteristic disturbances in hormone levels show the expected redistribution patterns.

Endocrine Regulation of Fetal Adipose Tissue Metabolism in the Pig: Role of Hydrocortisone

Glucocorticoids have been shown to be essential for the excessive fat deposition and development of obesity in several animal models. This study was performed to characterize the role of glucocorticoids in the developmental regulation of adipose tissue metabolism. On day 70 of gestation, pig fetuses were hypophysectomized by micro-cauterization. Hypophysectomized fetuses were implanted subcutaneously with hydrocortisone pellets or received no hormone replacement. Fetuses were removed by laparotomy on day 90 of gestation. Additional fetuses were hypophysectomized on day 70, implanted with hydrocortisone pellets on day 90 and removed on day 105 of gestation. Several intact fetuses were also implanted subcutaneously with hydrocortisone pellets during this later gestational period. Serum cortisol concentrations were reduced in hypophysectomized pigs at both fetal ages and were restored to intact levels by hydrocortisone treatment. Hydrocortisone supplementation enhanced lipolytic response to isoproterenol in intact fetuses but failed to restore lipolytic response to isoproterenol in hypophysectomized animals at either fetal age. Hydrocortisone induced a slight increase in lipogenesis in hypophysectomized fetuses when administered from 70 to 90 days of gestation and a more dramatic increase when administered from days 90 to 105 of gestation. However, hydrocortisone had no effect on basal or insulin stimulated lipogenesis in intact fetuses when administered from days 90 to 105 of gestation. These results indicate that hydrocortisone may have a primary influence on adipose tissue metabolism during late fetal development only in the absence of inhibition from counterregulatory hormones of pituitary origin.

Regulation of adipose tissue metabolism during pregnancy and lactation in the ewe: the role of insulin1

This study was conducted to examine the effect of insulin on lipid metabolism of adipocytes during pregnancy and lactation in ewes. During the first 3 mo of pregnancy, metabolism of adipocytes from omental adipose tissue was characterized by a high rate of de novo lipogenesis (90 to 125 nmol of acetate incorporated into lipids.2 h-1.10(6) cells-1) and a 38% reduction in response to beta-lipolytic stimulus (isoproterenol 10(-6) M). Simultaneously, there was a rise in the number of high-affinity insulin receptors (Kd = .2 nM), and insulin binding characteristics showed a decrease in the negative cooperativity phenomenon. Moreover, lipogenesis stimulated by insulin (1 mU/ml) increased in comparison with observations in nonpregnant ewes. The last third of pregnancy and early lactation were characterized by a marked fall in lipogenesis and a simultaneous increase in isoproterenol-stimulated lipolysis. During lactation, the number of total insulin receptors was decreased by 62% and insulin stimulation of lipogenesis became inefficient. Results suggest that insulin plays a direct role in adipose tissue metabolism during pregnancy.

Regulation of Adipose Tissue Metabolism in Support of Lactation

In the dairy cow, adipose tissue lipid accumulates during pregnancy, and catabolism begins prior to parturition and increases dramatically afterward. After peak lactation, body lipid is replenished. The duration and magnitudes of these adaptations depend on milk energy secretion, net energy intake, genotype, and endocrine environment. Recent research efforts have focused on endocrine, genetic, and biochemical mechanisms underlying metabolic adaptations in cows of high production potential. Adipose tissue lipid synthesis is decreased and lipolysis is increased in early lactation. The magnitude and duration of these adaptations are increased in animals either consuming relatively less energy or producing more milk. Adipose tissue is more responsive to catecholamines in early and midlactation and in animals with higher production. This is more of an increase in maximal response than in sensitivity. In vivo and in vitro rates of adipose tissue lipolysis correlate positively with milk energy secretion, whereas lipid synthesis rates correlate with energy intake. Thus, mammary metabolic activity, within and among lactations, correlates with that in adipose tissue. Likely mechanisms include adaptations in receptors for homeostatic signals and modulation of postreceptor responses. Research is needed into neural, genetic, and hormone regulation of nutrient utilization and body fat use and recovery during lactation. Research should describe mechanistic relationships among nutrients in animals of high production as well as investigate cellular and molecular mechanisms suitable to genetic manipulation.

Adipose tissue lipoprotein lipase activity in rats maintained at a reduced body weight

Male rats fed a cellulose-diluted diet maintained a reduced body weight. Adipose tissue lipoprotein lipase (LPL) activity decreased after two days of cellulose feeding, but was not different from chow-fed control levels with weight stabilized at 90% or 70% of the control group. Plasma triglyceride concentration decreased with weight loss and remained depressed with stabilized reduced weight. Regaining lost weight had no effect on LPL activity when compared with chow-fed controls or with levels obtained for the weight-reduced group. However, plasma triglyceride concentration returned to chow-fed control levels with weight gain. The disparity between these results and those obtained in obese human beings lends support to the hypothesis that the increase in adipose tissue LPL activity in weight-reduced obese human beings is indicative of a defect in regulation of adipose tissue metabolism.

Regulation of adipose tissue metabolism by catecholamines: roles of alpha 1, alpha 2 and beta-adrenoceptors

Regulation of adipose tissue metabolism by catecholamines: roles of alpha 1, alpha 2 and beta-adrenoceptors