Lipolysis: cellular mechanisms for lipid mobilization from fat stores.

The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels have revolutionized our understanding of lipolysis. In this review, we focus on the mechanisms that facilitate intracellular fatty-acid mobilization, drawing on canonical and noncanonical enzymatic pathways. We summarize how intracellular lipolysis affects lipid-mediated signalling, metabolic regulation and energy homeostasis in multiple organs. Finally, we examine how these processes affect pathogenesis and how lipolysis may be targeted to potentially prevent or treat various diseases.

Co-Administration of Soluble Fibres and Lactobacillus casei NCDC19 Fermented Milk Prevents Adiposity and Insulin Resistance Via Modulation of Lipid Mobilization Genes in Diet-Induced Obese Mice.

BACKGROUND: Numerous reports explaining the beneficial health effects of soluble fibres and probiotics on lifestyle disorders have been published. However, a little information is available on coadministration of soluble fibres such as gum acacia & inulin and probiotic lactobacilli. Therefore, in the present study, we have evaluated the synergistic effects of soluble fibres and probiotic fermented milk on adiposity, insulin resistance and dyslipidemia in C57BL/6 mice fed high-fat and sucrose diet for 18 weeks. OBJECTIVE: To explore the synergistic effect of soluble fibres (gum acacia/inulin) and Lactobacillus casei NCDC19 fermented milk on adiposity, insulin resistance and lipid mobilization genes in dietinduced obese mice. METHODS: C57BL/6 mice were divided randomly into three groups (n = 9/group) according to their body weights. The HFS group was fed high-fat and sucrose diet, the HFS-GFM group was fed HFS diet incorporated with gum acacia (7%, w/w) along with L. casei NCDC19 fermented milk and HFSIFM group was fed HFS diet incorporated with inulin (7%, w/w) along with L. casei NCDC19 fermented milk. RESULTS: At the end of the experiment, final body weight, epididymal fat (E.fat) weight, and adipocyte size were found to be lower in groups received either gum acacia or inulin in combination with L. casei NCDC19 fermented milk (HFS-GFM or HFS-IFM). Also, fasting blood glucose, serum insulin, triglycerides, and VLDL-cholesterol levels were decreased significantly in both HFS-GFM and HFSIFM fed groups. Furthermore, relative mRNA expression of genes (cpt1, foxa2, pgc1ß, and pparα) related to fatty acid oxidation enhanced significantly in the liver. In E.fat pad, expression of adiponectin was upregulated, whereas, leptin expression was reduced considerably. Also, expression of fasting-induced adipose factor enhanced significantly in the distal ileum of mice in HFS-GFM and HFS-IFM groups. CONCLUSION: Overall, we demonstrate that co-administration of soluble fibres viz. gum acacia, inulin and L. casei NCDC19 fermented milk exhibited the anti-adiposity effects, improved insulin sensitivity and dyslipidemia in mice via modulation of lipid mobilization genes.

Chrysanthemum Leaf Ethanol Extract Prevents Obesity and Metabolic Disease in Diet-Induced Obese Mice via Lipid Mobilization in White Adipose Tissue.

This study aimed to elucidate the molecular mechanism of Chrysanthemum morifolium Ramat. against obesity and diabetes, by comparing the transcriptional changes in epididymal white adipose tissue (eWAT) with those of the bioactive compound in C. morifolium, luteolin (LU). Male C57BL/6J mice were fed a normal diet, high-fat diet (HFD), and HFD supplemented with 1.5% w/w chrysanthemum leaf ethanol extract (CLE) for 16 weeks. Supplementation with CLE and LU significantly decreased the body weight gain and eWAT weight by stimulating mRNA expressions for thermogenesis and energy expenditure in eWAT via lipid mobilization, which may be linked to the attenuation of dyslipidemia. Furthermore, CLE and LU increased uncoupling protein-1 protein expression in brown adipose tissue, leading to energy expenditure. Of note, CLE and LU supplements enhanced the balance between lipid storage and mobilization in white adipose tissue (WAT), in turn, inhibiting adipocyte inflammation and lipotoxicity of peripheral tissues. Moreover, CLE and LU attenuated hepatic steatosis by suppressing hepatic lipogenesis, thereby ameliorating insulin resistance and dyslipidemia. Our data suggest that CLE helps inhibit obesity and its comorbidities via the complex interplay between liver and WAT in diet-induced obese mice.

Genipin ameliorates diet-induced obesity via promoting lipid mobilization and browning of white adipose tissue in rats.

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and ß-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.

Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice.

Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.

Short-term fasts increase levels of halogenated flame retardants in tissues of a wild incubating bird.

Many species are adapted for fasting during parts of their life cycle. For species undergoing extreme fasts, lipid stores are mobilized and accumulated contaminants can be released to exert toxicological effects. However, it is unknown if short-term fasting events may have a similar effect. The objective of this study was to determine if short successive fasts are related to contaminant levels in liver and plasma of birds. In ring-billed gulls (Larus delawarensis), both members of the pair alternate between incubating the nest for several hours (during which they fast) and foraging, making them a useful model for examining this question. Birds were equipped with miniature data loggers recording time and GPS position for two days to determine the proportion and duration of time birds spent in these two activities. Liver and plasma samples were collected, and halogenated flame retardants (HFRs) (PBDEs and dechlorane plus) and organochlorines (OCs) (PCBs, DDTs, and chlordane-related compounds) were determined. Most birds (79%) exhibited plasma lipid content below 1%, indicating a likely fasted state, and plasma lipid percent declined with the number of hours spent at the nest site. The more time birds spent at their nest site, the higher were their plasma and liver concentrations of HFRs. However, body condition indices were unrelated to either the amount of time birds fasted at the nest site or contaminant levels, suggesting that lipid mobilization might not have been severe enough to affect overall body condition of birds and to explain the relationship between fasting and HFR concentrations. A similar relationship between fasting and OC levels was not observed, suggesting that different factors are affecting short-term temporal variations in concentrations of these two classes of contaminants. This study demonstrates that short fasts can be related to increased internal contaminant exposure in birds and that this may be a confounding factor in research and monitoring involving tissue concentrations of HFRs in wild birds.

Panax red ginseng extract regulates energy expenditures by modulating PKA dependent lipid mobilization in adipose tissue.

Regulation of balance between lipid accumulation and energy consumption is a critical step for the maintenance of energy homeostasis. Here, we show that Panax red ginseng extract treatments increased energy expenditures and prevented mice from diet induced obesity. Panax red ginseng extracts strongly activated Hormone Specific Lipase (HSL) via Protein Kinase A (PKA). Since activation of HSL induces lipolysis in WAT and fatty acid oxidation in brown adipose tissue (BAT), these results suggest that Panax red ginseng extracts reduce HFD induced obesity by regulating lipid mobilization.

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation.

OBJECTIVE: Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation. DESIGN: Randomised placebo-controlled study. METHODS: In this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36  h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5  pmol/kg per min) or saline over 270  min. RESULTS: Obese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3ß-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (P<0.001), reduced excursions of 3 HB (P=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, P<0.0001) in all the three groups, but GH response was impaired in the obese subjects (P=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects. CONCLUSIONS: Despite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Effect of changes in fat availability on exercise capacity in McArdle disease.

BACKGROUND: The major fuel for exercising muscle at low exercise intensities is fat. OBJECTIVE: To investigate the role of fat metabolism in McArdle disease (also known as glycogen storage disease type V), an inborn error of muscle glycogenolysis, by manipulating free fatty acid availability for oxidation during exercise. DESIGN: Randomized, placebo-controlled, crossover trial. SETTING: Hospitalized care. PATIENTS: Ten patients (8 men and 2 women) with McArdle disease. INTERVENTIONS: Patients cycled at a constant workload corresponding to 70% of their maximum oxygen consumption. In random order and on separate days, patients received nicotinic acid (a known blocker of lipolysis) to decrease the availability of free fatty acids or 20% Intralipid infusion to increase free fatty acid availability during exercise. Results were compared with placebo (isotonic sodium chloride solution infusion) and glucose infusion trials. MAIN OUTCOME MEASURES: Exercise tolerance was assessed by heart rate response to exercise during different infusions. RESULTS: Free fatty acid levels more than tripled by Intralipid infusion and were halved by nicotinic acid administration. Heart rate was significantly higher during exercise in the Intralipid infusion and nicotinic acid trials compared with the placebo and glucose infusion trials, an effect that was observed before and after the patients had experienced the second wind phenomenon. CONCLUSIONS: Lipids are an important source of fuel for exercising muscle in McArdle disease, but maximal rates of fat oxidation seem limited and cannot be increased above physiologically normal rates during exercise. This limitation is probably caused by a metabolic bottleneck in the tricarboxylic acid cycle due to impaired glycolytic flux in McArdle disease. Therapies aimed at enhancing fat use in McArdle disease should be combined with interventions targeting expansion of the tricarboxylic acid cycle.

Site-related white adipose tissue lipid-handling response to oleoyl-estrone treatment in overweight male rats.

BACKGROUND: Oleoyl-estrone (OE) decreases energy intake while maintaining glucose homeostasis, and energy expenditure at the expense of body fat. White adipose tissue (WAT) depots behave differently under starvation, postprandial state and pharmacologically induced lipolysis. AIM OF THE STUDY: To understand the mechanism of massive lipid loss from WAT elicited by OE treatment. METHODS: We used overweight male rats. Rats receiving OE (10 nmol/g) gavages were compared with controls and a pair-fed group. Whole fat pads from the mesenteric, retroperitoneal, epididymal and inguinal subcutaneous sites were excised and analyzed for lipid, DNA, mRNA and the expression of lipogenic, fatty acid transporters and lipase genes. RESULTS: In OE and pair-fed rats, WAT weights decreased, with the limited loss of cells. Patterns of gene expression in most WAT sites were similar for OE and PF, suggesting a shared mechanism of fat mobilization, but in mesenteric WAT, PF increased lipogenic and fatty acid transporter gene expressions. However, OE inhibited lipogenic expressions more deeply than PF. CONCLUSIONS: White adipose tissue sites showed different expression patterns, hinting at relatively specialized functions in fat storage; thus, single site analyses cannot be extrapolated to whole WAT. Differences between mesenteric and the other sites suggest that 'visceral fat' should be reserved for this site only, and not applied to other abdominal fat depots (epididymal, retroperitoneal).

Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients.

CONTEXT: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extrapancreatic mechanisms. OBJECTIVE: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at an academic clinical research center. PATIENTS: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2), participated. INTERVENTION: INTERVENTION included 7 d treatment with the selective DPP-4 inhibitor vildagliptin or placebo and a standardized test meal on d 7. MAIN OUTCOME MEASURES: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin, dialysate glucose, lactate, pyruvate, glycerol were measured. RESULTS: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides, and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptin increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. CONCLUSIONS: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men.

Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a beta-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (alpha-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the alpha(2)-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the beta-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased alpha(2)-antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under beta-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.

Selective mobilization of fatty acids from adipose tissue in migratory birds.

During times of high energy demand, stored fatty acids are mobilized from adipocytes. This mobilization has previously been shown to be a non-random process, with more hydrophilic fatty acids being mobilized most readily. The objectives of this study were to characterize the relative mobilization of fatty acids from adipocytes in two migratory bird species and to investigate possible changes in selective fatty acid mobilization associated with the migratory period. Captive ruffs (Philomachus pugnax) and white-crowned sparrows (Zonotrichia leucophrys) were studied. The sparrows were divided into two treatments: 'winter' (photoperiod 8 h:16 h L:D) and 'migrant' (in which migratory condition was induced with a photoperiodic manipulation of 8 h:16 h L:D, followed by 16 h:8 h L:D). Adipose tissue was removed from ruffs and sparrows and incubated for 90 min after stimulation with epinephrine. The proportions of individual fatty acid species released into the incubation medium were compared with their proportions in the adipocytes to determine relative mobilizations. We found that patterns of relative mobilization in ruffs and sparrows are similar to those of mammals, with shorter chain lengths and more double bonds leading to higher relative mobilization. Seasonal condition in sparrows did not alter this pattern. This pattern of relative mobilization from adipocytes seems to be a general rule amongst birds and mammals and should be considered before inferring functionality about selective retention or mobilization of certain fatty acids. The composition of adipose stores in birds may affect migratory performance; however, our results indicate that patterns of relative mobilization at the adipocytes do not vary with season in migratory birds.

Sulfatides inhibit leukotriene synthesis in human polymorphonuclear granulocytes by a mechanism involving lipid rearrangement in intracellular membranes.

Sulfatides - sulfated derivatives of galactocerebroside - are endogenous ligands for P- and L-selectins and are able to induce intracellular signaling in neutrophils through a L-selectin dependent pathway. Sulfatides are implicated in a variety of physiological functions and have been found to suppress the synthesis of 5-lipoxygenase (5-LO) metabolites and impede 5-LO translocation to the nuclear envelope in adherent human polymorphonuclear leukocytes (PMNs) [Sud'ina, G. F., Brock, T. G., Pushkareva, M. A., Galkina, S. I., Turutin, D. V., Peters-Golden, M., et al. (2001). Sulphatides trigger polymorphonuclear granulocyte spreading on collagen-coated surfaces and inhibit subsequent activation of 5-lipoxygenase. The Biochemical Journal, 359, 621-629]. In this study we investigated the mechanism of the leukotriene (LT) synthesis inhibition by sulfatides. Sulfatides neither attenuated the ionophore-induced rise in [Ca(2+)](i) nor promoted PKA activation. We demonstrated that sulfatides directly inhibited 5-LO enzyme activity in a cell-free assay. BODIPY-labeled sulfatides were able to rapidly penetrate into the cells. Sulfatides induced rearrangement and redistribution of cytoskeletal components in adherent PMNs. The lipid incorporation as well as sulfatide-induced inhibition of LT synthesis were abolished by cytochalasin D, an inhibitor of actin polymerization and endocytosis. Importantly, sulfatides caused a prominent intracellular cholesterol redistribution, increasing its abundance at the uropod region. On the basis of these data, we suggest that increased cholesterol accumulation in cell compartments represents a novel mechanism by which sulfatides abrogate 5-LO translocation and activation.

The conjugated linoleic acid ester of estrone induces the mobilisation of fat in male Wistar rats.

We investigated whether the substitution of the fatty acid moiety in oleoyl-estrone (OE) by conjugated linoleic acid, i.e. conjugated linoleoyl-estrone (cLE) may help improve the antiobesity effects of OE. Overweight (17% fat) male rats were treated for 10 days with oral OE or cLE (10 nmol/g per day) and compared with controls receiving only the oily vehicle. Rat weight and food intake were measured daily. After killing by decapitation, body composition and main plasma parameters were analysed. cLE induced marked decreases in body weight, energy intake, carcass energy and body lipid, whilst sparing protein; the effects were not significantly different from those obtained with OE. Energy expenditure was unchanged, but energy intake decreased to 46% (OE) or 55% (cLE) of controls; whole body energy decreased by 29% (OE) or 24% (cLE) in the 10-day period studied. Plasma composition showed almost identical decreases in glucose and cholesterol elicited by OE and cLE, with a more marked decrease in triacylglycerols by OE and no effect of either on NEFA. OE decreased leptin and insulin levels, but the effects of cLE were more marked on both, with similar decreases in adiponectin. It can be concluded that cLE is a new drug of the OE family; its overall effects on energy were akin to those of OE, albeit fractionally less effective at the single dose tested. However, this lower potency on lipid mobilisation does not affect other effects, such as powerful hypercholesterolemic effects or the modulation of adiponectin. And last, but not least, cLE seems to produce a more marked decrease in leptin and insulin than OE, which may reflect a coordinate action of the conjugated linoleic acid moiety and the "OE effect" on target tissues. If that were the case, cLE may constitute an improvement over OE in its action on insulin resistance.

Morphological changes in the testis induced by diethylcarbamazine.

Diethylcarbamazine (DEC) had been proved to be highly effective against lymphatic filariasis, however its effect on vertebrate cells remains uncertain. After 12 days treatment with DEC, most of the Leydig cells were hypertrophied with several lipid droplets, and others had no nucleus and presented characteristic steatosis features. Vacuolization of Sertoli cells was also noted. Ultrastructural analyses of DEC-treated testes revealed spermatogonies with morphological characteristics of apoptosis, as shrinkage of cytoplasm and increased chromosomal density. In addition, Leydig cells showed numerous lipid droplets scattered throughout the cytoplasm, multivesicular bodies and giant whorl-like smooth endoplasmic reticulum. Several spermatids presented vacuolated mitochondriae, which were disorganized in relation to the microtubular axis of the flagellae. These results indicate that DEC probably affects the microtubular function, however the present data does not exclude the possibility that DEC also can act directly on enzymatic hormonal pathways.

Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise.

A series of polyphenols known as catechins are abundant in green tea, which is consumed mainly in Asian countries. The effects of catechin-rich green tea extract (GTE) on running endurance and energy metabolism during exercise in BALB/c mice were investigated. Mice were divided into four groups: nonexercise control, exercise control (Ex-cont), exercise+0.2% GTE, and exercise+0.5% GTE groups. Treadmill running time to exhaustion, plasma biochemical parameters, skeletal muscle glycogen content, beta-oxidation activity, and malonyl-CoA content immediately after exercise were measured at 8-10 wk after the initiation of the experiment. Oxygen consumption and respiratory exchange ratio were measured using indirect calorimetry. Running times to exhaustion in mice fed 0.5% GTE were 30% higher than in Ex-cont mice and were accompanied by a lower respiratory exchange ratio, higher muscle beta-oxidation activity, and lower malonyl-CoA content. In addition, muscle glycogen content was high in the GTE group compared with the Ex-cont group. Plasma lactate concentrations in mice fed GTE were significantly lower after exercise, concomitant with an increase in free fatty acid concentrations. Catechins, which are the main constituents of GTE, did not show significant effects on peroxisome proliferator-activated receptor-alpha or delta-dependent luciferase activities. These results suggest that the endurance-improving effects of GTE were mediated, at least partly, by increased metabolic capacity and utilization of fatty acid as a source of energy in skeletal muscle during exercise.

Combined effects of oleoyl-estrone and a beta3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats.

Oleoyl-estrone (OE) decreases appetite, induces adipose tissue wasting and resets the ponderostat setting, sparing glucose and protein. The beta3-adrenergic agonists increase energy expenditure and lipolysis. We studied the combination of both treatments to enhance fat mobilization. Overweight male rats received oral OE for 10 days; they were compared with controls and rats receiving a beta3-adrenergic agonist, CL316,243 (B3A); another group received both OE and B3A. Serum 3-hydroxybutyrate, NEFA, triacylglycerols and glucose showed only slight changes in all groups vs. controls; OE-treated rats showed lower cholesterol. OE decreased food intake and B3A increased energy expenditure. OE rats lost about 15%, B3A 24%, and those receiving both compounds lost 39% of their initial total body energy. In all cases, most of this energy imbalance was accounted for by the loss of body lipid. The combined treatment of OE and B3A reduced food intake, nevertheless maintaining a high energy expenditure. The combination of a beta3-adrenergic agonist with OE may help compensate the short-lived effects of the agonist and enhance the lipid mobilization action of OE. The eventual combination of both compounds should be explored as a way to obtain faster and more effective ways to treat obesity.

The effects of neurotensin on selected parameters of lipid metabolism in rats.

15 nM/kg b.m. of neurotensin (NT) caused a significant inhibition of LMA within 30 min of administration and this effect persisted up for to the 240 th minute of the experiment. A 15 nM/kgb.m. dose also caused a reduction in SLA which persisted up to the 120 th minute. Sixty minutes after an intraperitoneal administration of NT a decrease in the cholesterol and NEFA levels and an increase in the TG and glycerol levels were observed. These effects were inhibited by the NTR2-blocker (levocabastine) and were not subject to change after an in vivo application of SR 48692.

Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans.

CONTEXT: Atrial natriuretic peptide (ANP) in pharmacological concentrations stimulates lipid mobilization in humans. OBJECTIVE: The objective was to determine the hemodynamic and metabolic response to physiologically relevant ANP concentrations. DESIGN: The design was a human physiological study, conducted in 2004. SETTING: The study was conducted at an academic research institute. PARTICIPANTS: Fourteen healthy normal-weight men (30 +/- 1.2 yr) participated in the study. INTERVENTION: Intravenous infusion of human ANP (h-ANP) was administered at rates of 6.25, 12.5, and 25 ng/kg.min. MAIN OUTCOME MEASURES: We studied local changes in blood flow and glucose and lipid metabolism of abdominal sc adipose tissue and femoral skeletal muscle by microdialysis. Overall changes in energy expenditure and substrate oxidation rates were monitored by indirect calorimetry. RESULTS: The increase in serum nonesterified fatty acids and glycerol concentrations were correlated with ANP plasma concentrations (r(2) = 0.86 and r(2) = 0.76, respectively). In adipose tissue, glycerol increased from 53 +/- 6 micromol/liter to 87+/-13 micromol/liter (P < 0.001). In femoral skeletal muscle, glycerol concentrations did not change, whereas lactate-to-pyruvate ratio decreased from 91 +/- 23 to 32 +/- 4 (P < 0.001). Indirect calorimetry indicated an increase in lipid oxidation (P < 0.05) concomitantly with a decrease in carbohydrate oxidation (P < 0.01), without changes in overall energy expenditure. CONCLUSIONS: ANP briskly stimulates lipid mobilization and oxidation at plasma concentrations that are encountered in conditions such as heart failure. Natriuretic-peptide induced lipid mobilization might contribute to cardiac cachexia. Drugs that interfere with the natriuretic peptide system should be evaluated for potential metabolic side effects.