The enzymatic activities of bacterial isolates have been widely studied, but a spatial distribution of this activity is rarely focused. New antibiotic-producing microorganisms can be discovered in a more efficient manner if spatial statistical techniques are applied to the distribution of the activity of bacterial isolates in different terrains. This study is focused to generate a series of maps illustrating the spatial distribution of different soil parameters and the inhibition against relative-safe pathogens (like Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Salmonella, Pseudomonas fluorencens and Enterobacter cloacae) in an urban park in València (Spain). This spatial data has demonstrated a higher proportion of isolates was specifically allocated. This routine of data presentation is valuable for understanding bacterial population dynamics at a local level.

Paper recycling has increased in recent years. A principal consequence of this process is the problem of addressing polymeric components known as stickies. A deep characterization of stickies sampled over one year in a recycled paper industry in México was performed. Based on their chemical structure, an enzymatic assay was performed using lipases. Compounds found in stickies by Fourier-Transform Infrared spectrometry were poly (butyl-acrylate), dioctyl phthalate, poly (vinyl-acetate), and poly (vinyl-acrylate). Pulp with 4% consistency and pH=6.2 was sampled directly from the mill once macro stickies were removed. Stickies were quantified by counting the tacky macrostructures in the liquid fraction of the pulp using a Neubauer chamber before the paper was made, and they were analyzed with rhodamine dye and a UV lamp. Of the two enzymes evaluated, the best treatment condition used Lipase 30G at a concentration of 0.44 g/L, which produced a 35.59% decrease in stickies. SebOil DG showed a smaller stickies reduction of 21.5% when used at a concentration of 0.33 g/L. Stickies in kraft paper processes were actively controlled by the action of lipases, and future research should focus on how this enzyme recognizes its substrate and should apply synthetic biology to improve lipase specificity.

Enzymes serve as biocatalysts for innumerable important reactions; however, their application has limitations, which could be overcome by using appropriate immobilization strategies. Here, a new support for immobilizing enzymes is proposed. This hybrid organic-inorganic support is composed of chitosan—a natural, nontoxic, biodegradable, and edible biopolymer—and sodium polyphosphate, which was the inorganic component. Lipase B from Candida antarctica (CALB) was immobilized in microspheres by encapsulation using these polymers. The characterization of the composites (by infrared spectroscopy, thermogravimetric analysis, and confocal Raman microscopy) confirmed the hybrid nature of the support, whose external part consisted of polyphosphate and core was composed of chitosan. The immobilized enzyme had the following advantages: possibility of enzyme reuse, easy biocatalyst recovery, increased resistance to variations in temperature (activity declined from 60°C and the enzyme was inactivated at 80°C), and increased catalytic activity in the transesterification reactions. The encapsulated enzymes were utilized as biocatalysts for transesterification reactions to produce the compound responsible for the aroma of jasmine.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully un-derstood and causal treatment options are not available. Recently we demonstrated that Hepa-ranase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that As-pirin has inhibitory effect on Hpa. Another compound, which possesses a mild pan-creato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesize that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhib-itors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in ex-perimental model of AP induced by Cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the se-rum levels of Lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in heparanase transgenic (Hpa-Tg) mice vs wild-type (WT) mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Lipases have tremendous potential for industrial use, particularly, those mostly active against water-insoluble substrates, such as triglycerides composed of long-chain fatty acids. However, in most cases, mutants often need to be constructed to achieve optimal performance for such substrates. Protein engineering techniques have been reported as strategies for improving lipase characteristics by introducing specific mutations in the cap domain of esterases or in the lid domain of lipases, or through lid domain swapping. Here, we have improved the lipase character of a lipase, retrieved from the Marine Metagenomics MarRef Database and assigned to the Actinoalloteichus genus (WP_075743487.1), through site-directed mutagenesis and by substituting its lid domain (FRGTEITQIKDWLTDA) by the one of Rhizopus delemar (previously Rhizopus oryzae) lipase (FRGTNSFRSAITDIVF). Results demonstrated that the redesigned mutants gain activity against bulkier triglycerides such as glyceryl tridecanoate and tridodecanoate, olive oil, coconut oil, and palm oil. The absence of a residue in the new lid, present in the original lid, appears to be a key aspect to the increase in lipase character, although full activity recovery is only obtained with lid swapping.

The synthesis of new collagen, chitosan and chitosan-collagen coated magnetic nanoparticles have been done. Two types of cross-linkers for polymer shell stabilization were used: glutaraldehyde (Gla) as a standard cross-linker and new one – squaric acid (SqA). Structure and morphology of prepared nanoparticles were characterized by ATR-FT IR, XRD and TEM analysis. The immobilization of lipase from Candida rugosa was performed on the nanoparticles surface. The amount of immobilized enzyme was quantified by the Bradford method. All of lipase-biopolymers coated nanoparticles were characterized with good activity recovery. A little hyperactivation of lipase immobilized on nanoparticles with SqA was observed. All of prepared lipase-immobilized nanoparticles were characterized with very good reusability.

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore anti-obesity effect of A. bisporus extract (H2Oslim®) abundant in polysaccharides and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with H2Oslim® and chitosan. Treatment with H2Oslim® and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, H2Oslim® at 80 mg/kg body weight (BW)/day, and H2Oslim® at 160 mg/kg BW/day. H2Oslim® does-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high fat diet (HFD), an HFD with H2Oslim® at 80 mg/kg BW/day, H2Oslim® at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases of body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, H2Oslim® or chitosan administration ameliorated these increases. H2Oslim® or chitosan signifi-cantly reduced dietary efficiency and increased fecal excretion levels of lipid, triglyceride, and total cholesterol. These in vitro and in vivo findings suggest that H2Oslim® might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.

Background: Lipoprotein lipase (LPL) deficiency is a genetic condition. Affected individuals typically develop symptoms before age 10 with severe hypertriglyceridemia. No pharmacological treatment has lowered triglyceride levels in LPL deficiency patients successfully. The purpose of this study is to report on clinical outcomes of patients with LPL deficiency who responded to dietary therapy with successful reduction of their triglyceride (TG) levels with a long-chain triglyceride (LCT)-restricted, medium-chain triglyceride (MCT)-supplemented diet. Methods: A single-center retrospective case review study of LPL deficiency patients who met the inclusion criteria and were evaluated at the Hospital of Sick Children between January 2000 to December 2022. Data collected include demographic and clinical data, biochemical profiles at diagnosis and after dietary treatment initiation, and molecular results. Results: The study included seven patients with a suspected diagnosis of LPL deficiency (hypertriglyceridemia > 20 mmol/L). Six patients had a confirmed molecular diagnosis of LPL deficiency, and one had a Glycogen storage disease 1a (GSD1a) diagnosis. After presenting with hypertriglyceridemia, an LCT-restricted and MCT-supplemented diet was initiated, resulting in immediate and sustained TG reduction in all LPL deficiency patients that adhered to the diet. Additionally, they all maintained excellent growth and development. LPL deficiency-related complications were not observed under the MCT-enriched diet, except for increased pancreatic enzymes in one patient after dietary error. As expected, the diet failed to treat hypertriglyceridemia in the GSD1 patient. Conclusions: The dietary restriction of LCT in combination with MCT supplementation was feasible and effective in the long-term management of patients with LPL deficiency. In our experience, this treatment eliminated LPL-related complications and led to good clinical outcomes.

Obesity is a condition associated with the accumulation of excess fat in the body, energy imbalance, lipogenesis etc. which increases adipose tissue mass through adipogenesis and probes a health risk. Its prevalence has become a large burden on the world at large. One of the solutions to tackling obesity is with the use of bioactive compounds. We critically examined the effectiveness of hibiscus sabdariffa (HS) on various parameters associated with development of obesity such as; effect of HSE on body weight and energy expenditure, effect of HSE on fat accumulation, effect of HSE on lipase inhibition, effect of HSE on adipocyte differentiation/adipogenesis. This review has gathered reports on the various anti-obesity effects of HS bioactives in cell and animal models, as well as in humans. Reports have shown that hibiscus sabdariffa derived bioactives are potent in the treatment of obesity with evident reduction in body weight, inhibition of lipid accumulation and suppression of adipogenesis through PPARγ pathway and other transcriptional factors.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here we show that despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox [LPL KD]) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to WT controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of the free vs. bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in, or over-expressing, LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.

MAPLE (matrix assisted pulsed laser evaporation) depositions of Candida Rugosa lipase were carried out from ice matrices whose composition is optimized in order to minimize conformational damage of the protein, which strongly influences its catalytic activity. To induce lid opening and to protect lipase during the MAPLE process, pentane and m-DOPA amino acid were added to the liquid matrix giving a target formed by a frozen water-lipase-pentane microemulsion. FTIR and AFM were used to investigate the structure of MAPLE deposited lipase films. The ability of MAPLE films to promote transesterification was determined by thin layer chromatography. It was shown that m-DOPA has influence on the aggregation but not on the unfolding of lipase induced by MAPLE, while the microemulsion formed by the addition of pentane to the target composition is effective in protecting lipase during the MAPLE process. MAPLE deposited lipases showed a modified specificity.

Piceatannol (PIC), a natural analog of resveratrol, has various biological functions. We previously reported that PIC had an anti-obesity effect only in ovariectomized mice. While ovariectomized mice have low phosphorylation levels of hormone-sensitive lipase (pHSL) at Ser563, we found that PIC increased those levels. Here, we investigated the effect of PIC using 3T3-L1 adipocytes to clarify the mechanism by which PIC activates HSL. First, PIC was confirmed to induce HSL phosphorylation at Ser563 in 3T3-L1 cells as in vivo experiments showed. pHSL (Ser563) is believed to be activated through the β-adrenergic receptor (β-AR) and protein kinase A (PKA) pathway; however, the addition of a selective inhibitor of β-AR did not inhibit the effect of PIC. The addition of PKA inhibitor with PIC blocked pHSL (Ser563), suggesting that PIC’s effects are mediated by PKA from a different pathway than β-AR. The addition of G15, a selective inhibitor of the G protein-coupled estrogen receptor (GPER), lowered HSL activation by PIC. Furthermore, PIC inhibited insulin signaling and did not induce pHSL (Ser565), which represents its inactive form. This study is the first to suggest that the GPER pathway might regulate HSL activation in adipocytes.

This report demonstrates the first-time asymmetric synthesis of enantiopure structured triacylglycerols (TAGs) of the ABC type presenting three non-identical fatty acids, two of which unsaturated. The unsaturated fatty acids included the monounsaturated oleic acid (C18:1 n-9) and the polyunsaturated linoleic acid (C18:2 n-6). This was accomplished by a six-step chemoenzymatic approach starting from (R)- and (S)-solketals. The highly regioselective immobilized Candida antarctica lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. The synthesis also benefited from the use of the p-methoxybenzyl (PMB) ether protective group that enabled incorporation of two different unsaturated fatty acids to the glycerol skeleton. The total of six such TAGs were prepared, four constituting the unsaturated fatty acids in the sn-1 and sn-2 positions with a saturated fatty acid in the remaining sn-3 position of the glycerol backbone. In the two remaining TAGs the different unsaturated fatty acids accommodated the sn-1 and sn-3 end positions with the saturated fatty acid present in the sn-2 position. Enantiopure TAGs are urgently demanded as standards for enantiospecific analysis of intact TAGs in fats and oils.

Lipases, a versatile class of biocatalysts, have been shown to function in non-aqueous media/organic solvents and to possess promiscuous catalytic activity for a wide range of organic transformations. In this study, we explore the biocatalytic properties of a library of commercially available lipases by screening them for catalysis of a one-pot synthesis of Wieland-Miescher Ketone, an important intermediate in the synthesis of biologically active compounds such as steroids and terpenoids, from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. As a direct outgrowth of this screen, we have created an optimized procedure for Wieland-Miescher Ketone (WMK) synthesis using crude lipase preparations, characterizing both reaction yield and enantiomeric excess. We have also identified principal components of the crude lipase mixture through proteomics and present evidence for a non-lipolytic origin of the observed catalysis. Finally, using the optimized conditions developed in this study, we propose a general absorbance-based screening methodology for assessing biocatalytic potential of crude enzyme preparations for synthesis of WMK.

Polyphenols are well-known health promoting agents, but they have some limitations due to their spontaneous oxidation. This evidence has limited their use as drugs in the last years. In this field, several chemical modifications have been proposed to overcome these restrictions; among these, the esterification seems to be the preferred. Ester derivatives could be able to reduce the bioavailability problems connected to polyphenols. On the other hand, the presence of the esterase enzymes in the body guarantees the ester hydrolysis, which in turn frees the two molecules that make it up. Lipase-catalyzed esterifications afforded several derivatives of flavonoids glycosides, in green conditions. In this short note, pancreatic porcine lipase was firstly used as a cheap bio-catalyst, to synthesize oleoyl derivatives of quercetin in aglycone form. Results demonstrated how the enzyme acyl regioselective in position C-3, with high yields and easy purification processes

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

The -blocker (S)-practolol ((S)-N-(4-(2-hydroxy (isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the -blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)- 3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol was also produced in 53% yield, with 99% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. The yield of all four chlorohydrins increased by use of catalytic amounts of base. The reason for this was found to be less formation of the dimeric by-products compared to use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previous reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB) from SyncoZymes Co, Shanghai, China. Optical rotations confirmed the absolute configuration of the enantiopure drugs.

Esters are versatile compounds with a wide range of applications in various industries due to their unique properties and pleasant aromas. Conventionally, the manufacture of these compounds has relied on the chemical route. Nevertheless, this technique employs high temperatures and inorganic catalysts, resulting in undesired additional steps to purify the final product by removing solvent residues, which decreases environmental sustainability and energy efficiency. In accordance with the principles of “Green Chemistry” and the search for more environmentally friendly methods, a new alternative, the enzymatic route, has been introduced. This technique uses low temperatures and does not require the use of solvents, resulting in more environmentally friendly final products. In spite of the large number of studies published on the biocatalytic synthesis of esters, little attention has been paid to the reactors used for it. Therefore, it is convenient to gather the scattered information regarding the type of reactor employed in these synthesis reactions, considering the industrial field in which the process is carried out. The comparison between the performance of the different reactor configurations will allow us to draw the appropriate conclusions regarding their suitability for each specific industrial application.

As a consequence of intense industrialization in the last few decades, the amount of agro-industrial wastes has increasing, where new forms of valorization are crucial. In this work, 5 residual biomasses from Maranhão (Brazil) were investigted as supports for immobilization of lipase from Thermomyces lanuginosus (TLL). The new biocatalysts BM-TLL (babaçu mesocarp) and RH-TLL (rice husk) showed immobilization efficiencies >98% and hydrolytic activities of 5,331 U.g-1 and 4.608 U. g-1 respectively against 142 U. g-1 by Lipozyme® TL IM. High esterification activities were also found, with 141.4 U.g-1 and 396.4 U.g-1 from BM-TLL and RH-TLL against 113.5 U.g-1 by TL IM. Results of porosimetry, SEM and BET demonstrated BM and RH supports are mesoporous materials with large hydrophobic area, allowing a mixture of hydrophobic adsorption and confinement, resulting in hyperactivation of TLL. These biocatalysts were applied in the production of hexyl laurate, where RH-TLL was able to generate 94% conversion in 4 h. Desorption with Triton X-100 and NaCl confirmed that new biocatalysts were more efficient with 5 times less protein than commercial TL IM. All results demonstrated that residual biomass was able to produce robust and stable biocatalysts containing immobilized TLL with better results than commercial preparations.

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles compared to previously reported protocols.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.