Insulin increases cholesterol uptake, lipid droplet content, and apolipoprotein B secretion in CaCo-2 cells by upregulating SR-BI via a PI3K, AKT, and mTOR-dependent pathway.

The actions of insulin on intestinal cholesterol absorption and lipoprotein secretion are not well understood. Herein, we determined the effects of insulin on the levels of cholesterol transporter scavenger receptor, class B, type I (SR-BI), cellular cholesterol uptake, intracellular lipid accumulation, and lipoprotein secretion in a cellular model of human intestinal epithelium. METHODS: CaCo-2 cells were cultured to postconfluency in Transwell filters and stimulated with glucose (25 mM) in the presence or absence of insulin (100 nM) at their basolateral surface. SR-BI mRNA and protein levels were quantified by quantitative reverse transcription-PCR and immunoblot, respectively. Polarized localization of SR-BI was determined by cell surface proteins biotinylation and streptavidin precipitation. Activities of PI3K, AKT, mTOR, and SR-BI were pharmacologically antagonized. Cholesterol uptake was assessed by NBD-cholesterol incorporation. Apolipoprotein (apo) B concentration was quantified by ELISA. Subcellular localization of neutral lipids (BODIPY) and SR-BI (immunofluorescence) was determined by confocal microscopy. RESULTS: In polarized CaCo-2 cells, insulin increased SR-BI at the mRNA and protein levels. SR-BI was exclusively present at apical cell surface, as indicated by biotinylation and confocal microscopy analysis. Glucose did not modify SR-BI abundance or subcellular localization. Effects of insulin on SR-BI levels were abrogated by PI3K, AKT, or mTOR pharmacological antagonism. Cholesterol uptake, neutral lipid abundance, and apo B secretion were increased by insulin in CaCo-2 cells, and these effects were prevented by SR-BI pharmacological antagonism with block lipid transport-1. CONCLUSIONS: insulin promotes cholesterol uptake, intracellular lipid store, and apo B-containing lipoproteins secretion by SR-BI-dependent mechanisms in a model of human intestinal epithelium.

[Clinical presentation and treatment of primary lipodystrophies]. / Lipodistrofias primarias: presentación clínica y diagnóstico.

Lipodystrophies are a heterogeneous group of syndromes defined by a severe reduction of the adipose tissue. These can be congenital or acquired. Anatomically, they can be partial or generalized. The etiology of several lipodystrophies is well known. However, the cause of many others remains unknown. The commonest lipodystrophy worldwide is secondary to highly active anti-retroviral therapy in HIV-infected patients. By contrast, primary lipodystrophies (those not associated to any known disease or condition) are much less common and represent a diagnostic challenge. The major complications of lipodystrophies are metabolic, often resulting in severe insulin resistance, diabetes and dyslipidemia. No cure is available for lipodystrophies but the supplementation with recombinant leptin potently controls the metabolic abnormalities when there is a leptin deficiency. Herein, we review the clinical presentation, diagnostic process and therapeutic principles of the main primary lipodystrophy syndromes.

Nonalcoholic fatty liver disease, cholesterol gallstones, and cholecystectomy: new insights on a complex relationship.

PURPOSE OF REVIEW: Gallstone disease (GSD) and nonalcoholic fatty liver disease (NAFLD often coexist in a given patient and both conditions are associated to obesity and insulin resistance. The relationship between GSD and NAFLD is complex and bidirectional. In the present review, we summarize the existing information on the complex link between GSD and NAFLD and the potential implications for patient care. RECENT FINDINGS: Several clinical studies and systematic reviews have addressed the association between NAFLD and GSD underscoring that NAFLD is an independent risk factor for GSD. Conversely, GSD has been found also to be an independent risk factor for NAFLD with GSD potentially being linked to greater disease severity. In addition to the data showing association of NAFLD and GSD, recent evidence has also showed that cholecystectomy may itself be a risk factor for NAFLD development. The complex and bidirectional relationship between these diseases is partially explained by a number of common pathogenic links but the precise underlying mechanisms of the association of GSD and NAFLD need to be better delineated. Also, although the mechanisms of the promotional effect of cholecystectomy on NAFLD development are unknown, recent findings unveiling new aspects of gallbladder physiology and endocrine actions of bile acids provide a framework to advance research in this field. SUMMARY: In this review, we address the different aspects of the complex association between NAFLD and GSD. The potential underlying mechanisms and recent information on endocrine actions of bile acids and the gallbladder are reviewed.

Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients: a pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Experimental studies have shown that cholecystectomy (XGB) increases hepatic fat content in mice and appears associated to NAFLD in large retrospective population-based studies. The aim of this study was to prospectively assess the effects of XGB on hepatic fat content (HFC) and insulin resistance (IR) in non-obese, middle aged Hispanic subjects. METHODS: Twenty-six gallstone patients undergoing elective XGB and 16 control subjects with normal livers and gallbladders at ultrasonography were prospectively followed 24 months for changes in HFC and IR. Clinical, biochemical determinations and hepatic imaging were performed at baseline and 24 months after surgery. MRI technique quantified HFC in four hepatic segments. IR was assessed by the Homeostasis Model Assessment (HOMA-IR) index. RESULTS: Initial body mass index (BMI) was 25.6 ± 0.4 and 24.3 ± 1.0 in the control and XGB groups of subjects, respectively. Serum insulin level increased from 8.1 ± 0.7 to 10.0 ± 1.9 (µU/ml) 24 months after surgery in XGB patients (p < 0.05); no significant changes were detected in control individuals. Median HOMA-IR index increased from 1.31 (interquartile range, 1.01-1.68) to 2.20 (interquartile range, 1.57 - 2.60) 24 months after XGB, (p < 0.003). Median HOMA-IR index of control subjects remained unchanged at the end of the study. Serum apoB concentration increased from 61.5 ± 3.4 to 79.0 ± 7.8 (µg/ml) in XGB patients (p < 0.03). Serum apoB levels remained within normal ranges in both periods of the study in control subjects. HFC significantly increased in 2 of the 4 segments 24 months after XGB: right posterior hepatic lobe (from 5.3 ± 0.2% to 6.0 ± 0.2%, p > 0.04) and right anterior hepatic lobe (from 5.8 ± 0.2% to 6.6 ± 0.3%, p < 0.02). The average HFC of the four hepatic segments studied slightly increased from 5.4 ± 0.2 to 5.8 ± 0.3 2 years after XGB (p < 0.03). No significant changes were found in HFC in the control subjects at the end of the study. CONCLUSIONS: Elective XGB increases HFC, HOMA-IR index and serum apoB concentration. These results support the notion that XGB is a risk factor non-alcoholic fatty liver disease and other IR - associated disease conditions.

AGPAT2 deficiency impairs adipogenic differentiation in primary cultured preadipocytes in a non-autophagy or apoptosis dependent mechanism.

AIMS: Mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) result in lipodystrophy, insulin resistance and diabetes. Autophagy is required for normal adipogenesis and adipose tissue development. The aim of this study was to determine whether impaired autophagy or excessive cell death underlie the adipogenic inability of Agpat2(-/-) mice preadipocytes. METHODS: Preadipocytes were isolated from interscapular brown adipose tissue (BAT) of Agpat2(-/-) and Agpat2(+/+) newborn mice and cultured/differentiated in vitro. Intracellular lipids were quantified by oil red O staining. Cell death was assessed by lactate dehydrogenase (LDH) activity. Apoptosis and autophagy regulatory factors were determined at the mRNA and protein level with Real-time PCR, immunoblot and immunofluorescence. RESULTS: Adipogenically induced Agpat2(-/-) preadipocytes had fewer lipid-loaded cells and lower levels of adipocyte markers than wild type preadipocytes. Before adipogenic differentiation, autophagy-related proteins (ATGs) ATG3, ATG5-ATG12 complex, ATG7 and LC3II were increased but autophagic flux was reduced, as suggested by increased p62 levels, in Agpat2(-/-) preadipocytes. Adipogenic induction increased LDH levels in the culture media in Agpat2(-/-) preadipocytes but no differences were observed in the activation of Caspase 3 or in markers of autophagic flux. CONCLUSIONS: AGPAT2 is required for in vitro adipogenesis of mouse preadipocytes. Autophagy defects or apoptosis are not involved in the adipogenic failure of Agpat2(-/-) preadipocytes.

Reconstruction of laser-induced cavitation bubble dynamics based on a Fresnel propagation approach.

A single laser-induced cavitation bubble in transparent liquids has been studied through a variety of experimental techniques. High-speed video with varying frame rate up to 20×10(7) fps is the most suitable to study nonsymmetric bubbles. However, it is still expensive for most researchers and more affordable (lower) frame rates are not enough to completely reproduce bubble dynamics. This paper focuses on combining the spatial transmittance modulation (STM) technique, a single shot cavitation bubble and a very simple and inexpensive experimental technique, based on Fresnel approximation propagation theory, to reproduce a laser-induced cavitation spatial dynamics. Our results show that the proposed methodology reproduces a laser-induced cavitation event much more accurately than 75,000 fps video recording. In conclusion, we propose a novel methodology to reproduce laser-induced cavitation events that combine the STM technique with Fresnel propagation approximation theory that properly reproduces a laser-induced cavitation event including a very precise identification of the first, second, and third collapses of the cavitation bubble.

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2-/- lipodystrophic mice independent of hepatocyte leptin receptors.

Leptin is essential for energy homeostasis and regulation of food intake. Patients with congenital generalized lipodystrophy (CGL) due to mutations in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and the CGL murine model (Agpat2(-/-) mice) both have severe insulin resistance, diabetes mellitus, hepatic steatosis, and low plasma leptin levels. In this study, we show that continuous leptin treatment of Agpat2(-/-) mice for 28 days reduced plasma insulin and glucose levels and normalized hepatic steatosis and hypertriglyceridemia. Leptin also partially, but significantly, reversed the low plasma thyroxine and high corticosterone levels found in Agpat2(-/-) mice. Levels of carbohydrate response element binding protein (ChREBP) were reduced, whereas lipogenic gene expression were increased in the livers of Agpat2(-/-) mice, suggesting that deregulated ChREBP contributed to the development of fatty livers in these mice and that this transcription factor is a target of leptin's beneficial metabolic action. Leptin administration did not change hepatic fatty acid oxidation enzymes mRNA levels in Agpat2(-/-) mice. The selective deletion of leptin receptors only in hepatocytes did not prevent the positive metabolic actions of leptin in Agpat2(-/-) mice, supporting the notion that the majority of metabolic actions of leptin are dependent on its action in nonhepatocyte cells and/or the central nervous system.

[Association between diabetes mellitus and cardiovascular disease in Chilean adults: analysis of the National Health Survey 2009-2010]. / Asociación entre diabetes mellitus y patología cardiovascular en la población adulta de Chile: estudio de la Encuesta Nacional de Salud 2009-2010.

BACKGROUND: Diabetes mellitus (DM) is a recognized atherosclerotic cardiovascular disease (ACVD) risk factor. This association has yet to be quantified in the Chilean population. AIM: To compare the frequency of ACVD between diabetic and non-diabetic Chilean subjects. MATERIAL AND METHODS: Data was extracted from the Chile National Health Survey (ENS) performed in 2009-2010. DM diagnosis was made with fasting glucose. ACVD (coronary, cerebral and peripheral vascular disease) was established by self-report. Major cardiovascular risk factors were identified by clinical and laboratory assessment. RESULTS: A total of 5,416 adults (2,200 men and 3,216 women) were surveyed in ENS 2009-2010. Of these, 508 were diabetic and 375 reported ACVD. ACVD frequency was 16.1% and 6.1% in diabetic and non-diabetic subjects, respectively. In diabetic men, the frequency of ACVD steadily increased with age, from 5.1% to 22.1%. In diabetic women, the highest frequency of ACVD (17.4%) was found in ages ranging from 45 to 54 years. In people younger than 54 years, the odds ratio for ACVD in diabetic compared to non-diabetic subjects, was 3.59 in men (χ2 = 4.03 p < 0.03) and 5.26 in women (χ2 = 7.7 p < 0.007). Cardiovascular risk factors and metabolic syndrome were significantly more common in diabetic subjects with reported ACVD. CONCLUSIONS: DM is associated with an increased frequency of ACVD and cardiovascular risk factors in Chilean adults. In line with international reports, our findings suggest that DM is also a cardiovascular risk factor in Chile, particularly relevant for women.

[Novel physiological and therapeutic implications of leptin]. / Nuevas proyecciones fisiológicas, patológicas y terapéuticas de la leptina.

The adipose tissue is an endocrine organ that produces a variety of protein hormones. One of them is leptin, which regulates several critical functions at the central nervous system such as caloric intake, basal energy expenditure, reproduction, glucose and lipid metabolism and osteogenesis. Acting at a local level, leptin modulates the immune system and promotes liver fibrogenesis. The most promising therapeutic implications of leptin will possibly be in type 1 diabetes mellitus (DM1). Its supplementation in animal models of DM1 prevents hyperglycemia and ketoacidosis. These actions depend on the activation of leptin receptors in the central nervous system and the suppression of glucagon signaling in the liver.

Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD.

BACKGROUND AND AIM: The excessive accumulation of lipid droplets (LDs) is a defining characteristic of nonalcoholic fatty liver disease (NAFLD). The interaction between LDs and mitochondria is functionally important for lipid metabolism homeostasis. Exercise improves NAFLD, but it is not known if it has an effect on hepatic LD-mitochondria interactions. Here, we investigated the influence of exercise on LD-mitochondria interactions and its significance in the context of NAFLD. APPROACH AND RESULTS: Mice were fed high-fat diet (HFD) or HFD-0.1 % methionine and choline-deficient diet (MCD) to emulate simple hepatic steatosis or non-alcoholic steatohepatitis, respectively. In both models, aerobic exercise decreased the size of LDs bound to mitochondria and the number of LD-mitochondria contacts. Analysis showed that the effects of exercise on HOMA-IR and liver triglyceride levels were independent of changes in body weight, and a positive correlation was observed between the number of LD-mitochondria contacts and NAFLD severity and with the lipid droplet size bound to mitochondria. Cellular fractionation studies revealed that ATP-coupled respiration and fatty acid oxidation (FAO) were greater in hepatic peridroplet mitochondria (PDM) from HFD-fed exercised mice than from equivalent sedentary mice. Finally, exercise increased FAO and mitofusin-2 abundance exclusively in PDM through a mechanism involving the curvature of mitochondrial membranes and the abundance of saturated lipids. Accordingly, hepatic mitofusin-2 ablation prevented exercise-induced FAO in PDM. CONCLUSIONS: This study demonstrates that aerobic exercise has beneficial effects in murine NAFLD models by lessening the interactions between hepatic LDs and mitochondria, and by decreasing LD size, correlating with a reduced severity of NAFLD. Additionally, aerobic exercise increases FAO in PDM and this process is reliant on Mfn-2 enrichment, which modifies LD-mitochondria communication.

Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice.

Brown adipose tissue (BAT) is only present in mammals and has a thermogenic function. Brown adipocytes are characterized by a multilocular cytoplasm with multiple lipid droplets, a central nucleus, a high mitochondrial content, and the expression of uncoupling protein 1 (UCP1). BAT has been proposed as a potential therapeutic target for obesity and its associated metabolic disorders due to its ability to dissipate metabolic energy as heat. To investigate BAT function and regulation, brown adipocyte culturing is indispensable. The present protocol optimizes tissue processing and cell differentiation for culturing brown adipocytes from newborn mice. Additionally, procedures for the imaging of differentiated adipocytes with both confocal immunofluorescence and transmission electron microscopy are shown. In the brown adipocytes differentiated with the techniques described herein, the major defining features of classical BAT are preserved, including high UCP1 levels, increased mitochondrial mass, and very close physical contact between the lipid droplets and mitochondria, making this method a valuable tool for BAT studies.

The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour.

Nutritional, endocrine, and neurological signals converge in multiple brain centres to control feeding behaviour and food intake as part of the allostatic regulation of energy balance. Among the several neuroendocrine systems involved, the leptin, glucocorticoid, and glucagon-like peptide 1 (GLP1) systems have been extensively researched. Leptin is at the top hierarchical level since its complete absence is sufficient to trigger severe hyperphagia. Glucocorticoids are key regulators of the energy balance adaptation to stress and their sustained excess leads to excessive adiposity and metabolic perturbations. GLP1 participates in metabolic adaptation to food intake, regulating insulin secretion and satiety by parallel central and peripheral signalling systems. Herein, we review the brain and peripheral targets of these three hormone systems that integrate to regulate food intake, feeding behaviour, and metabolic homeostasis. We examine the functional relationships between leptin, glucocorticoids, and GLP1 at the central and peripheral levels, including the cross-regulation of their circulating levels and their cooperative or antagonistic actions at different brain centres. The pathophysiological roles of these neuroendocrine systems in dysregulated intake are explored in the two extremes of body adiposity - obesity and lipodystrophy - and eating behaviour disorders.

Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin.

BACKGROUND: Adipose tissue-derived stromal vascular fraction (SVF) harbors multipotent cells with potential therapeutic relevance. We developed a method to form adipose spheroids (AS) from the SVF with complex organoid structure and enhanced leptin secretion upon insulin stimulation. METHODS: SVF was generated from the interscapular brown adipose tissue of newborn mice. Immunophenotype and stemness of cultured SVF were determined by flow cytometry and in vitro differentiation, respectively. Spheroids were generated in hanging drops and non-adherent plates and compared by morphometric methods. The adipogenic potential was compared between preadipocyte monolayers and spheroids. Extracellular leptin was quantified by immunoassay. Lipolysis was stimulated with isoprenaline and quantified by colorimetric methods. AS viability and ultrastructure were determined by confocal and transmission electron microscopy analyses. RESULTS: Cultured SVF contained Sca1 + CD29 + CD44 + CD11b- CD45- CD90- cells with adipogenic and chondrogenic but no osteogenic potential. Culture on non-adherent plates yielded the highest quantity and biggest size of spheroids. Differentiation of AS for 15 days in a culture medium supplemented with insulin and rosiglitazone resulted in greater Pparg, Plin1, and Lep expression compared to differentiated adipocytes monolayers. AS were viable and maintained leptin secretion even in the absence of adipogenic stimulation. Glycerol release after isoprenaline stimulation was higher in AS compared to adipocytes in monolayers. AS were composed of outer layers of unilocular mature adipocytes and an inner structure composed of preadipocytes, immature adipocytes and an abundant loose extracellular matrix. CONCLUSION: Newborn mice adipose SVF can be efficiently differentiated into leptin-secreting AS. Prolonged stimulation with insulin and rosiglitazone allows the formation of structurally complex adipose organoids able to respond to adrenergic lipolytic stimulation.

Corrigendum: Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

[This corrects the article DOI: 10.3389/fendo.2023.1164047.].

Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

Introduction: The modern food environment facilitates excessive calorie intake, a major driver of obesity. Glucagon-like peptide 1 (GLP1) is a neuroendocrine peptide that has been the basis for developing new pharmacotherapies against obesity. The GLP1 receptor (GLP1R) is expressed in central and peripheral tissues, and activation of GLP1R reduces food intake, increases the expression of thermogenic proteins in brown adipose tissue (BAT), and enhances lipolysis in white adipose tissue (WAT). Obesity decreases the efficiency of GLP1R agonists in reducing food intake and body weight. Still, whether palatable food intake before or during the early development of obesity reduces the effects of GLP1R agonists on food intake and adipose tissue metabolism remains undetermined. Further, whether GLP1R expressed in WAT contributes to these effects is unclear. Methods: Food intake, expression of thermogenic BAT proteins, and WAT lipolysis were measured after central or peripheral administration of Exendin-4 (EX4), a GLP1R agonist, to mice under intermittent-short exposure to CAF diet (3 h/d for 8 days) or a longer-continuous exposure to CAF diet (24 h/d for 15 days). Ex-vivo lipolysis was measured after EX4 exposure to WAT samples from mice fed CAF or control diet for 12 weeks. . Results: During intermittent-short exposure to CAF diet (3 h/d for 8 days), third ventricle injection (ICV) and intra-peritoneal administration of EX4 reduced palatable food intake. Yet, during a longer-continuous exposure to CAF diet (24 h/d for 15 days), only ICV EX4 administration reduced food intake and body weight. However, this exposure to CAF diet blocked the increase in uncoupling protein 1 (UCP1) caused by ICV EX4 administration in mice fed control diet. Finally, GLP1R expression in WAT was minimal, and EX4 failed to increase lipolysis ex-vivo in WAT tissue samples from mice fed CAF or control diet for 12 weeks. . Discussion: Exposure to a CAF diet during the early stages of obesity reduces the effects of peripheral and central GLP1R agonists, and WAT does not express a functional GLP1 receptor. These data support that exposure to the obesogenic food environment, without the development or manifestation of obesity, can alter the response to GLP1R agonists. .

Sensory characterization of functional guava symbiotic petit cheese product.

The consumption of functional dairy products continues to rise due to consumer needs. This study aimed to develop a dairy guava functional symbiotic petit cheese product that included probiotics (Bifidobacterium animalis subsp. lactis BB-12, Chr. Hansen, Denmark) and prebiotics (inulin), which had adequate organoleptic characteristics. Moreover, adequate physicochemical, microbiological, and sensory characteristics during its shelf life were expected. A pasteurized skim milk curd flavored with a guava pulp was stabilized with gelatin to formulate this product. As sweeteners, iso maltol, erythritol, and Luo Han Guo extract from monk fruit (Siraitia Grosvenorii) were added. The prebiotic used was inulin, and the probiotic (Bifidobacterium animalis subsp. lactis BB-12, Chr. Hansen, Denmark). The product was kept refrigerated (4 °C) during the shelf life of 28 days. For the organoleptic analysis (100 consumers), the evaluations performed were: (1) overall liking (OL), (2) CATA (Check all that apply) testing 19 attributes, and (3) purchase intention was evaluated. Results were analyzed with FIZZ Software Biosystèmes. During shelf life, (1) physicochemical, microbiological, and sensory tests were performed. The product was evaluated as "liked much'' (7.16 out of 9); it was described as a creamy (71 %) natural product (73 %) with a fruity odor (57 %). It could be suitable for marketing because 82 % of the consumers would buy it. The product's probiotic character (over 1 × 106) was established through a microbiological count. On day one, the CFU was found to be 4.15 × 108, and after 28 days, 1.98 × 108 CFU of viable Bifidobacterium animalis subsp. lactis BB-12, leading us to establish its probiotic characteristics. The shelf life was estimated at 21 days.

Human 1-acylglycerol-3-phosphate O-acyltransferase isoforms 1 and 2: biochemical characterization and inability to rescue hepatic steatosis in Agpat2(-/-) gene lipodystrophic mice.

Loss-of-function mutations in 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) 2 in humans and mice result in loss of both the white and brown adipose tissues from birth. AGPAT2 generates precursors for the synthesis of glycerophospholipids and triacylglycerols. Loss of adipose tissue, or lipodystrophy, results in hyperinsulinemia, diabetes mellitus, and severe hepatic steatosis. Here, we analyzed biochemical properties of human AGPAT2 and its close homolog, AGPAT1, and we studied their role in liver by transducing their expression via recombinant adenoviruses in Agpat2(-/-) mice. The in vitro substrate specificities of AGPAT1 and AGPAT2 are quite similar for lysophosphatidic acid and acyl-CoA. Protein homology modeling of both the AGPATs with glycerol-3-phosphate acyltransferase 1 (GPAT1) revealed that they have similar tertiary protein structure, which is consistent with their similar substrate specificities. When co-expressed, both isoforms co-localize to the endoplasmic reticulum. Despite such similarities, restoring AGPAT activity in liver by overexpression of either AGPAT1 or AGPAT2 in Agpat2(-/-) mice failed to ameliorate the hepatic steatosis. From these studies, we suggest that the role of AGPAT1 or AGPAT2 in liver lipogenesis is minimal and that accumulation of liver fat is primarily a consequence of insulin resistance and loss of adipose tissue in Agpat2(-/-) mice.

Backscattering measurements from double-scale randomly rough surfaces.

We present experimental measurements of light backscattered from double-scale randomly rough surfaces (oceanlike surfaces) with different statistical parameters illuminated at small and large angles of incidence. The surfaces are composed of a small-scale roughness superimposed on a slowly (large-scale) varying surface. The large-scale surfaces are diamond-machined periodic surfaces made on aluminum substrates and have either a sinusoidal or a Stokes wave profile. The small-scale roughness is added with lithographic techniques, and the surfaces are then gold coated. For a linearly polarized incident beam, it is found that the backscattered light is strongly depolarized mainly at small angles of incidence and strong shadowing effects are present for large angles of incidence (θ(inc) > 60°).

[The contribution of Goldstein and Brown to the study of cholesterol metabolism]. / Rememorando la contribución de Goldstein y Brown al estudio del metabolismo del colesterol: a un cuarto de siglo del Premio Nobel de Medicina.

In December 1985, the Nobel Prize of Medicine was awarded to Drs. Joseph L. Goldstein and Michael S. Brown for their fundamental scientific work on the regulation of cholesterol metabolism mediated by the low density lipoprotein receptor pathway. This article briefly reviews the academic and research accomplishments of Drs. Brown and Goldstein as a tribute to these physician-scientists for their well-deserved award and enormous contribution to biomedical science worldwide.