Concentração de apolipoproteína A-1 (1.5±0.3; 1.5±0.2g/l). O tamanho da HDL também foi igual entre os dois grupos (8.8±0.8; 9.0±0.5 nm, respectivamente). A menopausa também não afetou a transferência de lípides da LDE para a HDL (em % total de radioatividade/10mg HDL/h), CE (0.5±0.3; 0.5±0.2, respectivamente), CL (0.9±0.2; 0.9±0.2), TG (0.6±0.2;0.6±0.2) e PL (3.0±0.7; 3.3±1.0). Conclusão: A menopausa não Introdução: A concentração plasmática da HDL é um fator de risco importante e independente para a prevenção da doença aterosclerótica, principalmente na mulher. Seu metabolismo e suas características estruturais e funcionais também têm sido estudados como fatores de risco. Neste estudo, foram comparadas mulheres de mesma faixa etária na pré e na pós-menopausa, para determinar a influência da menopausa sobre o tamanho da HDL e sobre a habilidade desta lipoproteína em receber lipídios de lipoproteínas doadoras, um processo que depende de proteínas de transferência e da composição e estrutura da HDL. Métodos: Vinte e duas mulheres saudáveis, normolipidêmicas na pré e dezoito na pós-menopausa, de idades entre 40-50 anos foram estudadas. Os grupos não diferiam em IMC, glicemia, colesterol total, LDL, triglicérides, apo A1 e apo B. Uma nanoemulsão artificial foi usada como modelo de LDL (LDE) para doar lípides para a HDL. LDE marcada radioativamente com 3 H-triglicérides (TG) e 14 C-colesterol livre (CL) ou 3 H- ésteres colesterol (CE) e 14 C-fosfolipídios (PL) foram incubados com as amostras de plasma por 1 hora. Após a precipitação química do sobrenadante contendo HDL, foi contada a radioatividade. O tamanho da HDL foi medido por espalhamento da luz laser. Resultados: A concentração da HDL nos dois grupos não diferiu, demonstrada pela concentração de HDL colesterol (61±12; 61±14 mg/dl respectivamente) e influenciou o tamanho das partículas HDL e um importante parâmetro funcional que é a habilidade da HDL de receber lipídios. / Objective: HDL levels are important for atherosclerosis prevention especially in the female gender, but functional aspects of the lipoprotein are also important. In this study, post-menopausal were compared to pre-menopausal women in the same age range to determine the influence of menopause upon the HDL size and ability of the lipoprotein to receive lipids from donor lipoproteins, a process that depends on transfer proteins and on HDL composition and structure. Methods: Twenty-two pre and eighteen postmenopausal, healthy and normolipidemic women, aged 40-50 yr. Both groups did not differ in BMI and plasma glucose, total and HDL cholesterol, triglycerides and apo B concentration. An artificial nanoemulsion (LDE) was used as a model of LDL to donate lipids to HDL. LDE labeled with 3 H-triglicerides (TG) and 14 C-free cholesterol (FC) or 3 H-cholesteryl esters (CE) and 14 C-phospholipids (PL) incubated with plasma samples for 1h. After chemical precipitation, the supernatant containing HDL was counted for radioactivity. HDL size was measured by laser-light-scattering. Results: HDL concentration of pre and post menopausal women did not differ as estimated by HDL cholesterol (61±12; 61±14 mg/dl respectively) and apo A1 concentration (1.5±0.3; 1.5±0.2g/l). HDL size also did not differ (8.8±0.8; 9.0±0.5 nm, respectively). Menopause also did not affect the transfer of lipids from LDE to HDL (in % of total radioactivity/10mg HDL/h), namely CE (0.5±0.3; 0.5±0.2, respectively), FC (0.9±0.2; 0.9±0.2), TG (0.6±0.2;0.6±0.2) and PL (3.0±0.7; 3.3±1.0). Conclusion: The menopause does not affect the size and an important functional parameter that is the ability of HDL to receive lipids.

A malária é uma doença que atinge 40% da população mundial e está entre as três maiores doenças infectantes do planeta, juntamente com a AIDS e a tuberculose. As crianças são as principais atingidas, uma vez que se estima que uma criança morra de malária a cada 40 segundos. As principais regiões atingidas são as que relacionam o clima tropical com altos índices de pobreza, como por exemplo a África sub-Sahariana. Este quadro agrava-se com o surgimento de cepas cloroquino-resistentes do Plasmodium falciparum, principal agente causador da malária grave. Muitos dos fármacos aplicados na terapêutica da malária apresentam inúmeros efeitos adversos, baixa biodisponibilidade e alta toxicidade, o que dificulta o emprego na terapêutica. Diante deste quadro urge o desenvolvimento de novos fármacos antimaláricos. A primaquina, fármaco desenvolvido na segunda guerra mundial, é o único esquizonticida tecidual disponível até o momento, porém apresenta baixa biodisponibilidade, em razão da meia-vida curta, e alta toxicidade. Estas características apresentadas pela primaquina podem ser atenuadas com o emprego da latenciação. O trabalho em questão visa ao desenvolvimento de pró-fármacos \"triglicerídicos\', também conhecidos com lipóides. Os pró-fármacos lipóides utilizam a digestão e absorção dos lipídeos para promover absorção, aumentando a biodiponibilidade e tempo de meia-vida, conseqüentemente, diminuindo a toxicidade. Serão sintetizados como transportadores os diglicerídicos dos ácidos palmítico, esteárico e decanóico. Estes ligar-se-ão à primaquina através dos espaçantes succnil, maleil e ftalil. / Abstract not available.

Elevadas concentrações de tirglicerídeos (TAG) no período pós-prandial são associados com o desenvolvimento de doenças cardiovasculares (DCV), bem como são responsáveis por mais de 23% da mortalidade em mulheres na menopausa. O treinamento de força (TF) é uma intervenção não farmacológica impregada na prevenção e redução dos múltiplos fatores de risco para o desenvolvimento de DCV. O exercício de força realizado em alto volume vem sendo apresentado como estratégia efetiva na redução da lipemia pós-prandial (LPP) em jovens. No entanto, a comparação entre alto e baixo volume do TF não havia sido investigado. Por esse motivo, o objetivo deste estudo foi comparar a resposta aguda e de 11 semanas de TF realizado em baixo e alto volume na força dinâmica máxima, espessura muscular, gasto energético e perfil lipidico de mulheres pós-menopáusicas. Trinta e nove mulheres pós-menopausicas saudáveis e destreinadas (59,5±4,8 anos de idade, massa corporal 69,6±9,1 kg, estatura 157,9±7,2 cm; IMC 27,6±4,1 kg•m2; circunferência da cintura 76,1±9,7 cm; VO2pico 18,7±1,4 mL•kg•min) foram aleatóriamente distribuídas em três grupos que realizaram a sessão de exercícios de força em: baixo volume (uma série) (BVEF, n=12), alto volume (AVEF, n=14) e um grupo controle (GC, n = 13) que permaneceu em repouso. Os grupos experimentais (BVEF e AVEF) foram submetidos a uma sessão de exercícios de força (SEF), envolvendo oito exercícios. O grupo BVEF realizou uma série de 15 repetições máximas (RM), e o grupo AVEF realizou três séries de 15RM. Na SEF foram avaliados o gasto energético da sessão e o EPOC (excess post-exercise oxygen consumption). No teste de tolerancia oral a gordura (TTOG), ~16 horas após a SEF, todos os grupos receberam um refeição hiperlipidica a base de leite seguido por uma avaliação do perfil lipídico (colesterol total (CT), glicose (GLU), HDL, LDL e TAG) nos períodos basal, 1, 2, 3, 4 e 5 horas após o TTOG. Resultados: Não houve diferença significativa entre os grupos no perfil lipidico em nenhum dos períodos avaliados. O gasto energético total (SEF+EPOC) foi significativamente maior para AVEF em comparação ao BVEF (6,0±0,12 MJ e 3,1±1,1 MJ, respectivamente, p<0,001). No estudo com treinamento, foram avaliadas trinta e seis mulheres pós-menopáusicas com uma perda amostral de três mulheres, sendo estas submetidas a 11 semanas de TF. Os grupos AVEF e BVTF foram divididos em alto volume de treinamento de força (AVTF=13) e baixo volume de treinamento de força (BVTF=12), o GC (n=11) foi preservado. Neste estudo, todas as variáveis foram avaliadas pré e pós treinamento. Como resultados; nenhuma diferença significativa foi observada entre os grupos na LPP (mmol/L/5hs) para GLU, HDL, LDL e CT. Além disso, o AVTF vs BVTF foi significativamente maior após 11 semanas de TF nas variáveis taxa de oxidação de gordura (5,52±1,69 g/h vs 4,11±1,12 g/h), espessura muscular (VM, 21,4 ± 1,8 mm vs 18,4±1,2 mm e VL (22,3±1,2 mm vs 20,8±1,3 mm). Os pontos 0, 1, 2, 4 e 5 horas após TTOG para TAG e AUC de TAG (5,79±0,42 mmol/L/5hs vs 7,78±0,68 mmol/L/5hs), respectivamente, foram significativamente menores no grupo AVTF (p<0,05). Em conclusão, diferentes volumes de uma única sessão de exercícios de força não são capazes de reduzir a lipemia pós-prandial de mulheres pósmenopáusicas após teste de tolerância a gordura. Entretanto, os resultados desta investigação sugerem que a prescrição do alto volume de treinamento de força reduz a lipemia pós-prandial em mulheres pós-menopáusicas. / Elevated concentrations of triglycerides (TAG) in the postprandial period are associated with the development of cardiovascular disease (CVD) and are responsible for over 23 % mortality in postmenopausal women. Resistance training (RT) is a non-pharmacological strategy to reduce multiple risk factors for developing CVD. The RT performed at high volume has been shown to be effective for the reduction of postprandial lipemia (PPL) in young people. However, the RT regular and systematic comparing high and low volume training had not been investigated. Therefore, the aim of this study was to compare the response subacute and 11 weeks of RT in low volume and high in strength, muscle thickness, energy expenditure and lipid profile of postmenopausal women. In article acute, thirty-nine postmenopausal women and healthy untrained (59.5±4.8 years, body mass 69.6±9.1 kg, height 157.9±7.2 cm, BMI 27,6±4.1 kg•m-2, waist circumference 76.1±9.7 cm; VO2peak 18.7±1.4 mL•kg-1•min-1) were randomly divided into three groups: group that conducted the exercise session strength at low volume (one set) ( LVSE, n=12), high volume (HVSE, n=14) and a control group (CG, n=13) who did not perform any exercise session. The experimental groups (LVSE and HVSE) held a session of strength exercises (SSE), involving eight exercises. In LVSE held a series of 15 repetitions maximum (RM), and the HVSE group performed three sets of 15RM, SSE were evaluated in the energy expenditure of the session and the EPOC (excess post -exercise oxygen consumption). In the test of oral fat tolerance (OGTT), ~16 hours of the SSE, all groups were given a high-fat meal and the milk, were evaluate; lipid profile (total cholesterol (TC), glucose (GLU), HDL, LDL and TAG) in times baseline, 1, 2, 3, 4 and 5 hours after an OGTT. Results: No significant difference between groups in lipid profile in any of the periods. Total energy expenditure (SSE+EPOC) was significantly higher compared to HVSE vs LVSE (6.0±0.12 MJ and 3.1±1.1 MJ, respectively, p<0.001). In the third study was evaluated thirty-six postmenopausal women, with a sample loss of three women who underwent 11 weeks of ST, and HVSE and LVSE groups were divided into high-volume strength training (HVST=13) and low volume strength training (LVST=12), GC (n=11) was preserved. In this study, all variables were assessed before and after 11 weeks os ST. Results: no significant difference was observed among groups in LPP (mmol/L/5 hours) to GLU, HDL, LDL and TC, also the HVSE versus LVSE was significantly greater after 11 weeks of ST for variables; rate fat oxidation, 5.52±1.69 g/h vs. 4.11±1.12g/h), muscle thickness (VM 21.4±1.2 mm versus 18.4±1.8 mm and VL, 22.3±1.2 mm versus 20.8±1.3 mm). In points 0, 1, 2, 4 and 5 hours after OGTT for TAG and TAG AUC (5.79±0.42 versus 7.78±0.68), respectively, were significantly lower in group AVTF (p<0.05). In conclusion, different volumes of a session of strength exercises do not reduce the subacutely postprandial lipemia in postmenopausal women after oral fat tolerance test. The results of this investigation suggest that the prescription of high volume strength training reduces postprandial lipemia in postmenopausal women.

Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-08-22T12:11:35Z No. of bitstreams: 1 2016 - Erica Bertha Fuhrich Raupp Bezerra de Mello.pdf: 1405623 bytes, checksum: 5fa531efb35b7236db276d4de4b56a2e (MD5) / Made available in DSpace on 2017-08-22T12:11:35Z (GMT). No. of bitstreams: 1 2016 - Erica Bertha Fuhrich Raupp Bezerra de Mello.pdf: 1405623 bytes, checksum: 5fa531efb35b7236db276d4de4b56a2e (MD5) Previous issue date: 2016-10-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Increased indicators of fat metabolism are found in Equine Metabolic Syndrome (EMS) subjects although these symptons are not included in the EMS definition described in the literature and in its diagnosis. 18 mares were allocated in three groups according to body condition status. In Group Ideal there were animals in fit condition (n=6), in Group Overweight, considered in overweight (n=6) and in Group Obese (n=6), animals considered obese. Fasting blood samples were taken to determine triglycerides, total cholesterol, glucose, and insulin concentrations in plasma. Insulin sensitivity proxy (RISQI) and ?-pancreatic secretion proxy (MIRG) were calculated from glucose and insulin data. There was a difference between groups in triglycerides levels (p<0.01), where Group Obese had significantly higher concentrations than other groups. Total cholesterol was higher in Group Obese compared to Group Ideal (p=0.01). No differences in plasma glucose (p=0.53) nor insulin (p = 0.10) concentrations and insulin sensitivity (RISQI: p=0.46) were seen among groups. Group Obese had a higher ?-pancreatic secretion (MIRG: p=0.05) compared to Group Ideal. The increased body condition score influenced the results of fat metabolites and ?-pancreatic secretion / O aumento das concentra??es de indicadores do metabolismo de gorduras ? bastante comum em casos diagnosticados de S?ndrome Metab?lica Equina (SME), mas apesar disto n?o entra no hall de fatores determinantes para diagn?stico da SME. Para avaliar a influ?ncia do escore corporal (EC) nas altera??es secund?rias associadas ? SME, foram avaliados lipidograma, glicemia, concentra??o de insulina, sensibilidade ? insulina (RISQI) e secre??o ?-pancre?tica de tr?s grupos de de ?guas Mangalarga Marchador n?o-getsantes/n?o-lactantes em tr?s diferentes categorias de EC (Ideal, Sobrepeso e Obeso). Cada grupo contou com 6 animais. Foram coletadas amostras de sangue em jejum de concentrado para a determina??o de concentra??o plasm?tica de triglicer?deos, colesterol total, glicose e insulina e a partir dos valores de glicemia e insulinemia foram calculados valores preditivos de sensibilidade ? insulina (RISQI) e secre??o ?-pancre?tica (MIRG). Houve diferen?a estat?stica entre os grupos quando avaliado os n?veis de triglicer?deos (p<0,01), sendo que o Grupo Obeso apesentou resultados significativamente superiores aos demais grupos. Foi observada diferen?a estat?stica entre os grupos quando avaliado as concentra??es de colesterol total (p=0,01), sendo que o Grupo Obeso apresentou resultados significativamente superiores ao Grupo Ideal. N?o foi observada diferen?a estat?stica entre os grupos nas concentra??es plasm?ticas de glicose (p=0,53) e insulina (p=0,10). N?o foi observada diferen?a estat?stica nos valores obtidos de RISQI (p=0,46), mas houve diferen?a estat?stica entre os grupos nos valores obtidos de MIRG (p=0,05), sendo que o Grupo Obeso obteve resultados significativamente superiores quando comparado com o Grupo Ideal. O escore corporal influenciou de forma positiva nos resultados do lipidograma e valor preditivo de secre??o ?-pancre?tica, sendo encontrados maiores n?veis em animais obesos.

A malária é uma doença que atinge 40% da população mundial e está entre as três maiores doenças infectantes do planeta, juntamente com a AIDS e a tuberculose. As crianças são as principais atingidas, uma vez que se estima que uma criança morra de malária a cada 40 segundos. As principais regiões atingidas são as que relacionam o clima tropical com altos índices de pobreza, como por exemplo a África sub-Sahariana. Este quadro agrava-se com o surgimento de cepas cloroquino-resistentes do Plasmodium falciparum, principal agente causador da malária grave. Muitos dos fármacos aplicados na terapêutica da malária apresentam inúmeros efeitos adversos, baixa biodisponibilidade e alta toxicidade, o que dificulta o emprego na terapêutica. Diante deste quadro urge o desenvolvimento de novos fármacos antimaláricos. A primaquina, fármaco desenvolvido na segunda guerra mundial, é o único esquizonticida tecidual disponível até o momento, porém apresenta baixa biodisponibilidade, em razão da meia-vida curta, e alta toxicidade. Estas características apresentadas pela primaquina podem ser atenuadas com o emprego da latenciação. O trabalho em questão visa ao desenvolvimento de pró-fármacos \"triglicerídicos\', também conhecidos com lipóides. Os pró-fármacos lipóides utilizam a digestão e absorção dos lipídeos para promover absorção, aumentando a biodiponibilidade e tempo de meia-vida, conseqüentemente, diminuindo a toxicidade. Serão sintetizados como transportadores os diglicerídicos dos ácidos palmítico, esteárico e decanóico. Estes ligar-se-ão à primaquina através dos espaçantes succnil, maleil e ftalil. / Abstract not available.

Abstract not available

Intramyocellular lipid (IMCL), an ectopic fat depot found within skeletal muscle fibers, is highly associated with obesity and strongly correlated with insulin resistance. IMCL accumulation in sedentary individuals may contribute to insulin resistance by interfering with insulin signaling in skeletal muscle, leading to inadequate glucose uptake by the cell. Lipid peroxidation is also associated with both obesity and insulin resistance, and with IMCL, but a relationship has yet to be established among all of these variables. The purpose of this project is to study for the first time the relationships among lipid peroxidation, IMCL content, and glucose uptake in skeletal muscle. Nine insulin-sensitive adults (IS), 13 insulin-resistant adults (IR), 10 diabetic (DB) and 8 subjects pre- and post- 12-week intervention with insulin-sensitizing thiazolinedione (TZD) were assessed for soleus IMCL with nuclear magnetic resonance, insulin sensitivity by both hyperinsulinemic-euglycemic clamp (GDR) and homeostasis model assessment index (HOMA1), and anthropometrics, including body mass index (BMI), percent fat by DEXA scan, and waist circumference. Vastus lateralis biopsies of all subjects were homogenized and analyzed by immunoblotting for post-translational protein modifications occurring from lipid-peroxidation (HNE). GDR and HOMA were significantly different among IS, IR, and DB groups, as expected, as were waist circumference and BMI. IMCL was significantly higher in DB than in IS and IR. HNE was also higher in DB than in IS, although it did not differ from IR. HNE was significantly correlated to GDR, HOMA1, and BMI, but not to IMCL, WAIST, or percent fat measures. IMCL showed a strong, negative correlation with GDR and was the primary, independent predictor of GDR in stepwise multiple regression. HNE was the primary, independent predictor of HOMA in stepwise multiple regression. Paired t-tests revealed improvements in insulin sensitivity measures after 12 weeks of TZD intervention, but no significant differences were observed in IMCL or HNE after intervention. These data show that skeletal muscle HNE and IMCL are both determinants of insulin resistance in obese, sedentary adults. HNE and IMCL are not related and therefore impact insulin resistance independently. These results reveal, for the first time, a negative relationship between skeletal muscle HNE and insulin sensitivity in sedentary individuals and underscore the importance of lipid peroxidation in insulin resistance.

The objective of this study was to examine the effects of a medium chain triglyceride oil mixture (MCTo), designed to increase energy expenditure and improve lipid profiles containing medium chain triglycerides, phytosterols and n-3 fatty acids in the form of flaxseed oil, versus the antioxidant alpha-lipoic acid (ALA). Forty-eight hamsters were fed (i) hypercholesterol emic (HC) control, (ii) HC MCTo, (iii) HC ALA, (iv) HC MCTo/ALA diets for 4 weeks. No effects on food intake, body weight, total body water, lean body mass, fat mass, and tissue thiobarbituric acid-reactive substances (TBARS) were observed. ALA alone had no effect on total cholesterol (TC); however, MCTo feeding increased TC with (p < 0.03) and without (p < 0.003) ALA when compared to control. ALA increased HDL levels compared to control (p 0.04) and MCTo/ALA (p < 0.007) groups. MCTo, with (p < 0.0001) or without (p < 0.006) ALA, increased non-HDL cholesterol levels versus control. The non-HDL:HDL ratio was decreased by ALA compared to MCTo (45%) and MCTo/ALA (68%) (p < 0.0001), a similar trend was seen when compared to the HC control (22%) group (p < 0.14). Triglyceride levels were not altered by any of the dietary treatments. Liver and heart tissue reduced glutathione (GSH) was increased (p < 0.05) by all three treatments when compared to control. Both tissues showed an increase (p < 0.05) in oxidized glutathione (GSSG) when fed ALA compared to all other treatments. Hamsters fed ALA had a lower (p < 0.05) GSH/GSSG ratio compared to all treatment groups. In conclusion, MCTo feeding does not elicit beneficial effects on circulating plasma lipids and measures of body composition. In addition, our results do not clearly support an improvement in oxidative status through supplementation of ALA. However, our results do support the existence of beneficial effects of ALA on circulating lipoprotein content in the hamster.

Recent research has shown that the combination of high triglyceride (TG) levels and low high density lipoprotein (HDL) levels, significantly increases the incidence of coronary artery disease (CAD). The incidence of CAD is also increased in abdominally obese individuals. To assess differences in postprandial TG clearance patterns between abdominally obese (AO) and controls (C), fourteen healthy, normolipidemic males (seven controls and seven abdominally obese) completed an oral fat loading test (78 grams of fat). Blood samples were collected every hour for eight hours. Abdominally obese individuals had significantly greater TG values, significantly lower total HDL and HDL2 values and significantly greater area under the TG curve (p = 0.03). Time to reach peak TG and time to reach baseline TG values did not differ between the two groups, even though fewer AO individuals reached baseline within eight hours. The data from the present investigation indicate that increased time to clear TG in AO individuals may be one pathway that increases the incidence of CAD in this group. / School of Physical Education

Individuals with high levels of plasma triglycerides are at high risk to develop cardiovascular disease (CVD), currently one of the major causes of death worldwide. Recent epidemiological studies show that loss-of-function mutations in the APOC3 gene lower plasma triglyceride levels and reduce the incidence of coronary artery disease. The APOC3 gene encodes for apolipoprotein (APO) C3, known as an inhibitor of lipoprotein lipase (LPL) activity. Similarly, a common gain-of-function mutation in the LPL gene is associated with reduced risk for CVD. LPL is central for the metabolism of lipids in blood. The enzyme acts at the endothelial surface of the capillary bed where it hydrolyzes triglycerides in circulating triglyceride-rich lipoproteins (TRLs) and thereby allows uptake of fatty acids in adjacent tissues. LPL activity has to be rapidly modulated to adapt to the metabolic demands of different tissues. The current view is that LPL is constitutively expressed and that the rapid modulation of the enzymatic activity occurs by some different controller proteins. Angiopoietin-like protein 4 (ANGPTL4) is one of the main candidates for control of LPL activity. ANGPTL4 causes irreversible inactivation through dissociation of the active LPL dimer to inactive monomers. Other proteins that have effects on LPL activity are the APOCs which are surface components of the substrate TRLs. APOC2 is a well-known LPL co-factor, whereas APOC1 and APOC3 independently inhibit LPL activity. Given the important role of LPL for triglyceride homeostasis in blood, the aim of this thesis was to find small molecules that could increase LPL activity and serve as lead compounds in future drug discovery efforts. Another aim was to investigate the molecular mechanisms for how APOC1 and APOC3 inhibit LPL activity. Using a small molecule screening library we have identified small molecules that can protect LPL from inactivation by ANGPTL4 during incubations in vitro. Following a structure-activity relationship study we have synthesized lead compounds that more efficiently protect LPL from inactivation by ANGPTL4 in vitro and also have dramatic triglyceride-lowering properties in vivo. In a separate study we show that low concentrations of fatty acids possess the ability to prevent inactivation of LPL by ANGPTL4 under in vitro conditions. With regard to APOC1 and APOC3 we demonstrate that when bound to TRLs, these apolipoproteins prevent binding of LPL to the lipid/water interface. This results in decreased lipolysis and in an increased susceptibility of LPL to inactivation by ANGPTL4. We demonstrate that hydrophobic amino acid residues that are centrally located in the APOC3 molecule are critical for attachment of this protein to lipid emulsion particles and consequently for inhibition of LPL activity. In summary, this work has identified a lead compound that protects LPL from inactivation by ANGPTL4 in vitro and lowers triglycerides in vivo. In addition, we propose a molecular mechanism for inhibition of LPL activity by APOC1 and APOC3.