The Physiological and Pathological Role of Acyl-CoA Oxidation.

Fatty acid metabolism, including ß-oxidation (ßOX), plays an important role in human physiology and pathology. ßOX is an essential process in the energy metabolism of most human cells. Moreover, ßOX is also the source of acetyl-CoA, the substrate for (a) ketone bodies synthesis, (b) cholesterol synthesis, (c) phase II detoxication, (d) protein acetylation, and (d) the synthesis of many other compounds, including N-acetylglutamate-an important regulator of urea synthesis. This review describes the current knowledge on the importance of the mitochondrial and peroxisomal ßOX in various organs, including the liver, heart, kidney, lung, gastrointestinal tract, peripheral white blood cells, and other cells. In addition, the diseases associated with a disturbance of fatty acid oxidation (FAO) in the liver, heart, kidney, lung, alimentary tract, and other organs or cells are presented. Special attention was paid to abnormalities of FAO in cancer cells and the diseases caused by mutations in gene-encoding enzymes involved in FAO. Finally, issues related to α- and ω- fatty acid oxidation are discussed.

The Role of Acyl-CoA ß-Oxidation in Brain Metabolism and Neurodegenerative Diseases.

This review highlights the complex role of fatty acid ß-oxidation in brain metabolism. It demonstrates the fundamental importance of fatty acid degradation as a fuel in energy balance and as an essential component in lipid homeostasis, brain aging, and neurodegenerative disorders.

Increased Amount of Polyunsaturated Fatty Acids in the Intestinal Contents of Patients with Morbid Obesity.

INTRODUCTION: Obesity is associated with disturbed gut microbiota homeostasis that translates into altered intestinal and blood metabolite profiles. The long-chain fatty acid (LCFA) may be absorbed in the intestine, but until now, their composition in intestinal contents of patients with obesity has not been studied. The aim of the present study was to verify whether obesity is related to any changes in fecal LCFA content and whether intestinal LCFA content may be associated with the health status of patients with obesity. METHODS: The fatty acid composition has been studied in stool samples obtained from 26 patients with morbid obesity and 25 lean subjects by gas chromatography-mass spectrometry. The dietary habits were assessed using the Food Frequency Questionnaire (FFQ-6). RESULTS: Our results show for the first time that lean subjects and patients with obesity differ in their stool LCFA profiles. The levels of most n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs were significantly higher in fecal samples from people with obesity than in those from lean controls. CONCLUSIONS: Based on the current knowledge, we have defined three hypotheses that may explain proving the cause-and-effect relationships observed differences in fecal LCFA profiles between patients with obesity and lean subjects. They may be related to alterations in fat digestion and/or LCFA absorption and diet. However, proving the cause-and-effect relationships requires further research.

The Pathophysiological Role of CoA.

The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.

Acyl-Coenzyme A: Cholesterol Acyltransferase Inhibition in Cancer Treatment.

Overexpression of acyl-coenzyme A:cholesterol acyltransferase (ACAT) results in increased cholesteryl ester levels and has been involved in a variety of cancer types. As a consequence, cholesterol metabolism has raised interest as a potential target for cancer treatment. Inhibition of ACAT results in suppression of proliferation in a range of cancer cell types both in vitro and in vivo. The exact mechanism of this phenomenon is being investigated, and the most important findings are presented in this review.

In Vivo Effectiveness of Orlistat in the Suppression of Human Colorectal Cancer Cell Proliferation.

BACKGROUND/AIM: Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. MATERIALS AND METHODS: Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. RESULTS: Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 µM. CONCLUSION: Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.

Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue.

BACKGROUND: Cumulating evidence underlines the role of adipose tissue metallothionein (MT) in the development of obesity and type 2 diabetes. Fasting/refeeding was shown to affect MT gene expression in the rodent liver. The influence of nutritional status on MT gene expression in white adipose tissue (WAT) is inconclusive. The aim of this study was to verify if fasting and fasting/refeeding may influence expression of MT genes in WAT of rats. RESULTS: Fasting resulted in a significant increase in MT1 and MT2 gene expressions in retroperitoneal, epididymal, and inguinal WAT of rats, and this effect was reversed by refeeding. Altered expressions of MT1 and MT2 genes in all main fat depots were reflected by changes in serum MT1 and MT2 levels. MT1 and MT2 messenger RNA (mRNA) levels in WAT correlated inversely with serum insulin concentration. Changes in MT1 and MT2 mRNA levels were apparently not related to total zinc concentrations and MTF1 and Zn transporter mRNA levels in WAT. Fasting or fasting/refeeding exerted no effect on the expression of MT3 gene in WAT. Addition of insulin to isolated adipocytes resulted in a significant decrease in MT1 and MT2 gene expressions. In contrast, forskolin or dibutyryl-cAMP (dB-cAMP) enhanced the expressions of MT1 and MT2 genes in isolated adipocytes. Insulin partially reversed the effect of dB-cAMP on MT1 and MT2 gene expressions. CONCLUSIONS: This study showed that the expressions of MT1 and MT2 genes in WAT are regulated by nutritional status, and the regulation may be independent of total zinc concentration.

Progesterone-induced down-regulation of hormone sensitive lipase (Lipe) and up-regulation of G0/G1 switch 2 (G0s2) genes expression in inguinal adipose tissue of female rats is reflected by diminished rate of lipolysis.

Decreased lipolytic activity in adipose tissue may be one of the reasons behind excess accumulation of body fat during pregnancy. The aim of this study was to analyze the effect of progesterone on the expression of: (a) Lipe (encoding hormone-sensitive lipase, HSL), (b) Pnpla2 (encoding adipose triglyceride lipase, ATGL), (c) abhydrolase domain containing 5 (Abhd5), and (d) G0/G1 switch 2 (G0s2) genes in white adipose tissue (WAT), as potential targets for progesterone action during the course of pregnancy. Administration of progesterone to female rats, which was reflected by approximately 2.5-fold increase in circulating progesterone concentration, is associated with a decrease in Lipe gene expression in the inguinal WAT. The expression of Pnpla2 gene in all main fat depots of females and males remained unchanged after progesterone administration. Administration of progesterone resulted in an increase in the expression of Abhd5 gene (whose product increases ATGL activity) and G0s2 gene (whose product decreases ATGL activity) in the inguinal WAT of female rats. Mifepristone, a selective antagonist of progesterone receptor, abolished the effect of progesterone on Lipe, Abhd5 and G0s2 genes expression in the inguinal WAT. The decrease in Lipe and the increase in Abhd5 and G0s2 genes expression was associated with lower rate of stimulated lipolysis. Administration of progesterone exerted no effect on Lipe, Abhd5 and G0s2 genes expression and stimulated lipolysis in the retroperitoneal WAT of females, as well as in the inguinal, epididymal and retroperitoneal WAT of males. In conclusion, our findings suggest that progesterone decreases the rate of lipolysis in the inguinal WAT of female rats, inhibiting the activity of both ATGL (by stimulating synthesis of G0S2 - specific inhibitor of the enzyme) and HSL (due to inhibition of Lipe gene expression).

Enhanced food intake by progesterone-treated female rats is related to changes in neuropeptide genes expression in hypothalamus.

INTRODUCTION: Progesterone-treated females eat more food, but the mechanism underlying this effect is not well understood. The aim of the study was to analyse the effect of progesterone on neuropeptide genes expression in rat hypothalamus. MATERIAL AND METHODS: Experiments were carried out on female and male Wistar rats. Animals were treated with progesterone (100 mg per rat) for 28 days. NPY and CART mRNA levels in hypothalamus were quantified by real-time PCR. The serum progesterone concentration was determined by radioimmunoassay. RESULTS: Progesterone administration to females caused an increase in food intake, body mass, and white adipose tissue mass. Elevated circulating progesterone concentration up-regulated NPY and down-regulated CART genes expression in hypothalamus of females. In males, elevated blood progesterone concentration had no effect on food intake, body and fat mass and on the neuropeptide genes expression in hypothalamus. Moreover, administration of progesterone in females resulted in decrease of PR mRNA level in hypothalamus. No effect of progesterone administration on PR mRNA level in hypothalamus of males was found. CONCLUSIONS: The changes in neuropeptide genes expression in hypothalamus may lead to stimulation of appetite and might explain the observed increase in food intake, body and adipose tissue mass in progesterone-treated females.

Chemerin gene expression is regulated by food restriction and food restriction-refeeding in rat adipose tissue but not in liver.

Chemerin is an adipokine that regulates adipocyte development and metabolism as well as inflammatory and immune function of some cells. Although chemerin may be linked to obesity and related diseases, little is known about the nutritional regulation of chemerin gene expression. We investigated the effect of prolonged food restriction, a common approach in treating obesity and related diseases, and prolonged food restriction-refeeding on chemerin gene expression in rat white adipose tissue and liver. The prolonged food restriction was accompanied by an approximately 2-fold decrease in chemerin mRNA level in rat white adipose tissue. Upon refeeding, an increase (approximately 8-fold as compared to rats maintained on restricted diet and 4-fold as compared to control) in chemerin mRNA level in white adipose tissue was found. Surprisingly, no effect of food restriction and food restriction-refeeding on chemerin mRNA level in the liver was found. Chemerin mRNA level in adipose tissue was positively correlated with serum insulin concentration. Moreover insulin increased significantly chemerin gene expression in primary rat adipocytes. The changes in chemerin mRNA level in adipose tissue and serum chemerin concentrations were associated with changes in serum leptin and free fatty acid concentrations. Collectively, the data presented here indicate that chemerin gene expression is regulated by nutritional status in rat adipose tissue but not in liver. It seems that insulin plays important role in stimulation of chemerin gene expression in adipose tissue. However, changes in serum leptin and free fatty acids concentrations after food restriction-refeeding suggest that the role of these factors in the regulation of chemerin gene expression in adipose tissue cannot be excluded. Lack of the effect of food restriction and food restriction-refeeding on liver chemerin gene expression suggests that adipose tissue is the dietary modifiable source of serum chemerin concentration.

Up-regulation of lipogenic enzyme genes expression in inguinal white adipose tissue of female rats by progesterone.

Contradictory results have been published regarding the influence of progesterone on lipids metabolism in adipose tissue. The aim of the present work was to elucidate whether progesterone administration in the setting of an experimental model influences lipogenic enzyme genes expression, body and adipose tissue mass. The results presented here indicate that the elevated blood progesterone concentration was associated with significant increase in lipogenic enzyme genes expression in inguinal adipose tissue of females. The rise in the expression of lipogenic enzyme genes was associated with an increase in sterol regulatory element binding transcription factor 1 (Srebf1) and S14 genes expression. Mifepristone, a specific antagonist of progesterone receptor, abolished progesterone's effect on body mass, inguinal fat mass, and lipogenic enzyme genes expression in inguinal adipose tissue. No significant changes were found in the expression of lipogenic enzyme genes, Srebf1 and S14 genes in perirenal white adipose tissue of females. The elevated blood progesterone concentration was associated with the increase in body and inguinal white adipose tissue mass of females. In males, elevated blood progesterone concentration had no effect on the lipogenic enzyme genes expression and on body and fat mass. In conclusion, we demonstrate that a chronic increase in serum progesterone concentration in females was associated with up-regulation of lipogenic enzyme genes expression in inguinal adipose tissue. Up-regulation of Srebf1 and S14 genes expression following progesterone administration suggests that products of these genes might be involved in the regulation of lipogenic enzyme genes expression by progesterone. The stimulatory effect of progesterone on lipogenic enzyme genes expression in inguinal adipose tissue seems to be specific as it was reversed by specific antagonist of progesterone receptor.

The gender- and fat depot-specific regulation of leptin, resistin and adiponectin genes expression by progesterone in rat.

Progesterone affects lipid metabolism in adipose tissue and influences fat distribution in human. The aim of the study was to analyze the effect of progesterone on rat body and fat mass and on expression of genes encoding adipokines involved in the regulation of energy homeostasis. The results presented here indicate that progesterone administration to females caused increase in body and inguinal white adipose tissue mass. The increase of inguinal white adipose tissue mass is associated with the hypertrophy of adipocyte. The same dose of progesterone caused increase of its circulating concentration in males, however it barely reached the value observed in non-treated control females and did not have any effect on body and fat mass. The elevated circulating progesterone concentration was associated with an approximately 6- and 2-fold increase of leptin and resistin mRNA level respectively, and 2-fold decrease of adiponectin mRNA level only in inguinal white adipose tissue of females. RU 486, specific antagonist of progesterone receptor, abolished the effect of progesterone on the adipokine mRNA level in inguinal adipose tissue. In males, the elevated circulating progesterone concentration showed no effects on leptin, resistin or adiponectin mRNA level in inguinal, retroperitoneal or epididymal adipose tissue. Moreover, the results presented in this paper demonstrate a relatively high level of progesterone receptor mRNA in inguinal white adipose tissue of females, which was down-regulated in response to progesterone administration. In retroperitoneal adipose tissue of control females progesterone receptor mRNA level was approximately 3-fold lower as compared to inguinal adipose tissue. In inguinal, epididymal and retroperitoneal white adipose tissue of males progesterone receptor mRNA was hardly detected. Our results suggest that depot- and sex-dependent responsiveness of adipose tissue to the pharmacological dose of progesterone is controlled by both circulating concentration of progesterone and the white adipose tissue progesterone receptor level.

Differential effect of prolonged food restriction and fasting on hypothalamic malonyl-CoA concentration and expression of orexigenic and anorexigenic neuropeptides genes in rats.

Several lines of evidence suggest that malonyl-CoA in the hypothalamus plays an important role in monitoring and modulating body energy balance. In fasted state the level of malonyl-CoA concentration significantly decreases. Simultaneously, orexigenic neuropeptides (NPY - neuropeptide Y, AgRP - agouti-related peptide) genes are expressed at high level, whereas anorexigenic neuropeptides (CART - cocaine-and amphetamine-regulated transcript, POMC - proopiomelanocortin) genes are expressed at low level. When food intake resumes, opposite effect is observed. This study examined the effect of prolonged food restriction, common in humans trying to lose body weight on expression of orexigenic and anorexigenic neuropeptides genes and on malonyl-CoA content in rat whole hypothalamus. We observed an increase of NPY and AgRP mRNA levels in hypothalamus of rats kept on 30 days-long food restriction (50% of the amount of food consumed by controls). Simultaneously, a decrease of CART and POMC mRNA levels occurred. Refeeding caused a decrease in NPY and POMC mRNA levels without effect on AgRP and CART mRNA. Surprisingly, both prolonged food restriction and food restriction/refeeding caused the increase of malonyl-CoA level in whole hypothalamus. In contrast, fasting for 24h caused the decrease of malonyl-CoA level, which was associated with the up-regulation of NPY and AgRP genes expression and down-regulation of CART and POMC genes expression. After refeeding opposite effect was observed. These results indicate that prolonged food restriction and acute fasting, conditions in which energy expenditure exceeds intake, differentially affect malonyl-CoA concentration and similarly affect orexigenic and anorexigenic neuropeptide genes expression in whole rat hypothalamus.

Refeeding after prolonged food restriction differentially affects hypothalamic and adipose tissue leptin gene expression.

Rat adipose tissue is the principal site of leptin synthesis, however, leptin gene expression has been demonstrated in many rat tissues. Some data indicate that leptin produced by human brain and adipose tissue could cooperate in the regulation of food intake. In this case the regulation of leptin gene expression in hypothalamus and in adipose tissue should be coordinately regulated. Food restriction is often undertaken by many humans trying to lose body weight. Thus, the current study was aimed to analyze whether leptin gene expression in rat hypothalamus and in adipose tissue is regulated synchronously by prolonged food restriction and prolonged food restriction/refeeding. We demonstrate here that although leptin gene is expressed at very low level in rat hypothalamus, its expression in hypothalamus was down-regulated by prolonged food restriction similarly as in the white adipose tissue. Refeeding after prolonged food restriction caused both an increase of leptin gene expression in white adipose tissue and the increase in serum leptin concentration. In contrast, no significant effect of prolonged food restriction/refeeding on hypothalamic leptin gene expression was observed. The reduction of leptin gene expression in both hypothalamus and white adipose tissue by prolonged food restriction was associated with a significant increase of NPY gene (a target of leptin signaling) expression in hypothalamus. Refeeding after prolonged food restriction caused the decrease of NPY gene expression in hypothalamus, however NPY mRNA level remained higher than in controls. The results presented in this paper indicate that prolonged food restriction/refeeding differentially affects leptin gene expression in adipose tissue and in hypothalamus. Moreover, obtained data suggest that in rats leptin synthesized in hypothalamus exerts marginal effect on NPY gene expression and on serum leptin concentration.

Surgical removal of perirenal and epididymal adipose tissue decreases serum leptin concentration and increases lipogenic enzyme activities in remnant adipose tissue of old rats.

BACKGROUND: The rate of lipogenesis and gene expression of lipogenic enzymes in white adipose tissue (WAT) of rats decreases with age. Previously, we showed the inverse relationship between serum leptin concentration and lipogenic enzymes activities in WAT of ageing rats. Based on those results, we postulated that leptin could play some role in the downregulation of lipogenic enzyme genes expression in WAT of old rats. OBJECTIVE: To further test this hypothesis, in the present paper we examined the effect of surgical removal of perirenal and epididymal WAT on serum leptin concentration and lipogenic enzymes activities in remnant adipose tissue of old rats. METHODS: One-year-old rats, which display a high serum leptin concentration and low lipogenic enzyme activities in WAT, were subjected to surgical removal of the perirenal and epididymal WAT. Two months after the surgery, the serum leptin concentration and lipogenic enzyme activities in remnant WAT were compared to the serum leptin concentration and lipogenic enzyme activities measured in adipose tissue collected during the surgery. RESULTS: WAT removal resulted in an approximately 6-fold decrease of serum leptin concentration and about a 2-fold increase of lipogenic enzyme activities in remnant adipose tissue. CONCLUSIONS: These results indicate that interventions designed to reduce abdominal adipose tissue mass can change the lipogenic activity of remnant adipose tissue. Additionally, leptin could be one of the factors contributing to the downregulation of the genes expression of lipogenic enzymes during ageing in rats.

[The important role of GLUT2 in intestinal sugar transport and absorption]. / Kluczowe znaczenie nosnika GLUT 2 w transporcie glukozy w komórkach jelit.

The classical model of sugar absorption indicates that Na+ -glucose cotransporter, SGLT1 transports glucose from intestinal lumen to cytosol and GLUT2 transports glucose from cytosol to the blood. Recent evidence indicates that GLUT 2 is rapidly inserted into the apical membrane after a meal. Intestinal glucose absorption by the apical GLUT2 pathway can be 3 to 5-times greater then by SGLT1 et the high concentration of sugar. Apical GLUT2 insertion is regulated by pathway of calcium absorption through L-type channel Ca(v)1.3, activation of sweet taste receptors (T1R2/F1R3) and endocrine and paracrine hormones (especially insulin and GLP-2).

Serum adiponectin and leptin concentrations in patients with chronic pancreatitis of alcoholic and nonalcoholic origin.

OBJECTIVE: The aim of this study was to assess serum adiponectin and leptin concentrations in patients with chronic pancreatitis of alcoholic and nonalcoholic origin. METHODS: Forty-four male patients with chronic pancreatitis of alcoholic origin and 10 patients of nonalcoholic origin as well 16 healthy subjects were examined. Fasting blood samples were collected. Serum adiponectin, leptin, and insulin concentrations were determined by radioimmunoassay methods. RESULTS: Patients with chronic pancreatitis had lower body mass index values compared with those of control. Nonetheless, there were no differences in serum adiponectin concentration between pancreatitis patients and healthy controls. Pancreatitis patients had lower serum leptin and insulin concentrations than healthy subjects. No difference in serum leptin and insulin concentrations between patients with chronic pancreatitis of alcoholic and nonalcoholic origin was observed. The serum adiponectin/leptin concentration ratio was higher in chronic pancreatitis patients than in control subjects. CONCLUSIONS: Chronic pancreatitis in humans (a) is associated with the decrease in serum leptin and insulin concentrations, (b) does not affect serum adiponectin concentration but increases serum adiponectin/leptin concentration ratio, and (c) alters the interrelationship between serum adiponectin and insulin concentrations. Moreover, these results suggest that changes in serum leptin and insulin concentrations are independent on the etiology of chronic pancreatitis.

Up-regulation of rat adipose tissue adiponectin gene expression by long-term but not by short-term food restriction.

Beneficial effects of food restriction as well as elevated circulating adiponectin concentration on the cardiovascular system, lipid metabolism and non-insulin dependent diabetes have been reported. The present article indicates that the reduction in rat body and adipose tissue weight after long-term (1 month) food restriction (either 75% or 50% of ad libitum food intake) was accompanied by the increase in serum adiponectin concentration. The increase in serum adiponectin concentration is the result of the significant increase in white adipose tissue adiponectin gene expression. In contrast to long-term food restriction, short-term (3 days) food restriction (either 75% or 50% of ad libitum food intake) did not influence body and fat mass as well as serum adiponectin concentration and white adipose tissue adiponectin mRNA level. The obtained results suggest that long-term food restriction is necessary to increase in serum adiponectin concentration that could be beneficial, to prevent some disorders associated with low serum adiponectin concentration like obesity and obesity-related diseases.

Chronic food restriction differentially affects NPY mRNA level in neurons of the hypothalamus and in neurons that innervate liver.

Neuropeptide Y (NPY) is found in neurons of the brain and in the neurons that innervate abdominal organs including liver. Major biological function of hypothalamic NPY is regulation of appetite and body weight homeostasis. In the periphery, biological function of NPY varies, depending on the organ/tissue. Increased hypothalamic NPY mRNA level in response to chronic caloric restriction is a well documented phenomenon. The effect of food restriction on NPY mRNA level in neurons that innervate liver has not been published so far. To evaluate how chronic food restriction affects liver (and other abdominal organs) NPY mRNA level, we compared NPY mRNA abundance in liver, kidney cortex, perirenal white adipose tissue and in hypothalamus of rats maintained on chronic restricted diet. Data presented in this paper indicate that chronic food restriction: (a) caused the increase of NPY mRNA level in the hypothalamus, (b) caused the decrease of NPY mRNA level in the liver, and (c) was without effect on NPY mRNA level in kidney cortex and perirenal white adipose tissues. Moreover, rats maintained on restricted diet displayed lower serum NPY, leptin and insulin concentrations and higher serum corticosterone concentration. Together, these data suggest that hypothalamus and liver (and other abdominal organs) NPY gene expression is differentially regulated by caloric restriction. It seems that liver NPY gene expression in contrast to the hypothalamus NPY gene expression is not suppressed by leptin.

[Regulation of extramitochondrial malic enzyme gene expression in lipogenic tissues]. / Regulacja ekspresji genu cytosolowego enzymu jablczanowego w narzadach lipogennych.

Extramitochondrial malic enzyme is widely distributed in mammalian tissues, including humans. The major role of this protein in the liver and white adipose tissue is the production of NADPH required for fatty-acid synthesis. Malic enzyme thus belongs to the family of lipogenic enzymes. Malic enzyme activity is regulated both by gene transcription and mRNA stability. Malic enzyme gene expression is tightly controlled by hormonal (i.e. insulin, glucagon, triiodothyronine) and nutritional conditions. There are many transcription factors which recognize special response elements present in the malic enzyme gene promoter. In this paper some important information about the structure and regulation of malic enzyme gene expression in mammalian lipogenic tissues is presented.