Obesity Metabolic Disorders Research Articles

Hookworm infection aggravates metabolic disorder in obesity

Obesity and ancylostomiasis are considered public health problems. Recent studies have shown that infection by intestinal helminths in obese individuals can ameliorate metabolic disorder and improve glucose tolerance by decreasing both insulin resistance and low-intensity inflammation. However, few helminth species have been studied in this context, and some modulation mechanisms still require deeper investigation. Therefore, the present work aimed to investigate the role of experimental infection with Ancylostoma ceylanicum in the modulation of the immune response in an obese experimental model. Four groups of hamsters were used as follows: two groups were submitted to a hyperlipidic and hypercaloric diet capable of inducing obesity, one infected and the other uninfected; and two normonourished control groups, one infected and one uninfected by A. ceylanicum. Biochemical, haematological, parasitological and immunological parameters were evaluated. The results demonstrated that A. ceylanicum infection accentuated weight loss in obese animals compared to normonourished animals. However, obesity reduced the recovery of worms and oviposition of the females, and both infected groups showed decreased levels of haemoglobin, albumin, iron and erythrocytes. Significant relations were observed for pathogenesis in the following cases: infection interfered in lipid metabolism, which increased levels of total cholesterol and triglycerides in the obese group, and caused a decrease in HDL levels in both groups. Obesity led to an increase in glucose levels, and the infection exacerbated this parameter in both the normonourished and obese groups. Inflammation was intensified in obese animals that showed elevated macrophage and neutrophil activation in adipose tissue, enlargement of the spleen and accumulation of lipids in the liver and faeces. Despite the decrease in IFN-γ levels, the infection did not potentiated the expression of the Foxp3, IL-10 and IL-2 transcription factor for any of the infected groups, markers that could positively compensate the host from the damage caused by obesity.

The effect of hypercaloric diet and Quercetin on the full-transcriptome liver tissue profile of Zucker-LEPRfa rats

BACKGROUND: The peptidic hormone leptin (Lep) occupies a central place in the control of energy homeostasis and body weight in mammals. A convenient model for studying the role of impaired Lep reception is the Zucker-LEPRfa rats, which carry a mutation in the homozygote of the LEPR gene. Quercetin (Q; 3.3 ‘, 4’, 5.7-pentahydroxyflavone) is currently being considered as one of the promising biologically active substances, which allows to correct metabolic disorders in obesity and metabolic syndrome.
 AIM: to study changes in the expression of genes in liver tissue of rats with impaired receptivity of Lep under the influence of high-fat and high-carbohydrate diet (HFCR) or/and Q supplementation.
 MATERIAL AND METHODS: 4 groups of six male Zucker-LEPRfa male rats were used in experiment. Within 61 days the animals of the 1st group (control) received a balanced semi-synthetic diet, the second group received the same diet with the addition of quercetin in a dose of 50 mg/kg of body weight, the third group — the HFCR (30% fat by dry weight and 20% fructose instead of water), the 4th group is the same diet and supplement of quercetin. Full transcriptional profiling of liver tissue was performed on microchips from the Gene Expression Hybridization Kit (Agilent Technologies), a real-time polymerase chain reaction combined with reverse transcription (RT-PCR) was performed for liver transcripts of Crot, FTO, NpY, Prdx1, Prom1, Ugt2b37 and GAPDH genes contained in liver tissue.
 RESULTS: It was shown that feeding of Zucker-LEPRfa rats with Q and/or HFCR led to significant changes in the level of transcription of 1604 genes in liver tissue, from which the effect of quercetin proper was manifested for 1396 genes. Changes were more pronounced in the transcriptome of liver tissue caused by HFCR, than caused by the addition of Q against the background of a standard diet. Q influenced the expression of genes responsible for xenobiotic detoxification processes (UGT2b37), redox homeostasis (Prdx1), beta-oxidation of fatty acids (Crot), and central mechanisms affecting hunger and satiety (NpY), and potentiated, or abolished the effects of HFCR against a number of other functionally important genes. Bioinformatic analysis revealed the influence of HFCR and/or Q on 23 metabolic pathways (KEGGS), of which 7 (the metabolism of steroids, arachidonic and linoleic acids, retinoids, drugs and xenobiotics (due to cytochrome P-450), bile secretion) were affected in all experimental groups.
 CONCLUSIONS: Changes in the transcriptome of the liver of Zucker-LEPRfa rats, caused by consumption of HFCR and/or Q, were consistent with experimental data on changes in short-term memory, anxiety and mineral metabolism in these animals.

Effect of quercetin on the expression of the carbohydrate and lipid metabolism genes in the liver of rats with genetic

Quercetin (Q; 3,3',4',5,7-pentahydroxyflavone) is considered as a promising component of specialized products for the correction of metabolic disorders in obesity and metabolic syndrome. At the same time, the results of evaluating the clinical efficacy of Q are ambiguous, and the mechanisms of its influence on lipid and carbohydrate-energy metabolism are not well understood. The aim of the work was to study the effect of quercetin (Q 3,3',4',5,7-pentahydroxyflavone) on the expression of key glycolysis and lipogenesis enzymes' genes in Zucker-Leprfa (Z) rats characterized by hereditary obesity, compared to «wild-type» Wistar (W) rats. Material and methods. 24 male Z rats and 32 male W rats aged 8-10 weeks were used. Animals of each line were divided into 4 groups of equal numbers. For 62 days the animals of the first groups (controls) received a balanced diet according to AIN93M, the seconds - the same diet with Q added in a dose of 50 mg/kg body weight. Animals of the third groups received a high-fat, high-carbohydrate diet (HFCD) with fat 30% by weight and with the replacement of drinking water with a 20% solution of fructose, the fourths groups - the same diet and supplementation with Q. After removing animals from the experiment, expression levels of liver carbohydrate and lipid metabolism genes Khk, Gck, Pklr, Acaca, Fasn, Scd, Srebf1, Mlxipl, Ppara and Pparg were determined by real-time polymerase chain reaction (RT-PCR) with reverse transcription using Actb and Gapdh as reference genes. The levels of triglycerides, total and HDL cholesterol, lipolytic activity and immunoreactive leptin were determined in plasma. Results and discussion. When comparing two animal lines, a significantly higher level of expression of Ppara, Pparg, Mlxipl, Acaca, Fasn, Scd was shown in Z rats compared to W rats, which is consistent with the development of dyslipidemia in the first ones and elevated levels of leptin under both types of diets used. The addition of Q caused in W rats a decrease in the expression of Scd, Mlxipl, Khk and Gck, more pronounced on the background of HFCD whereas in Z rats there were no similar effects, or they had the opposite direction. In addition, in Z rats, consumption of Q led to increased expression of Pklr, which was not observed in W rats. Conclusion. The modulating effect of Q on the expression of key genes of lipid and carbohydrate metabolism enzymes significantly differs in wild-type W rats and mutant Z rats with hereditary obesity, and this difference appears to be potentiated by the consumption of excess fat and fructose.

Moringa Oleifera improve lipid metabolic disorders in obesity induced oxidative stress in rats

Moringa Oleifera leaves have therapeutic functions such as antioxidant, anti-bacterial, anti-viral, anti-cancer, anti-inflammatory, anti-allergic and anti-diabetic. The purpose of this study was to evaluate the protective effect of Moringa Oleifera on obesity induced oxidative stress and biochemical abnormalities in male rats. Forty-eight male albino rats were divided into three equal groups. Group I (control normal): rats fed normal diet. Group II (Obesity): rats received high fat diet (HFD).Group III (Obesity+ Moringa oleifera): rats received Moringa Oleifera (600 mg/kg.b.wt.) orally for two months after induction of obesity. The obtained results showed significant increase in levels of serum insulin, lipids profile (total cholesterol and triacylglycerols), liver L-MDA in addition to up regulation of Leptin and Nuclear factor kappa B (NF-κB) gene expression level in obese rats. However, liver catalase activity and GSH concentration were markedly decreased. Moringa Oleifera treatment to high fat diet-induced obesity in rats caused significant improvement of all previous parameters towards its normal ranges. These results suggested that, Moringa Oleifera treatment exerts a protective effect on obesity by reduction of oxidative stress markers, inflammation and hyperlipidemia in rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.

Neuromediators and neuropeptides: the biomarkers for metabolic disturbances in obesity

The role of biogenic amines (serotonin, dopamine) and neuropeptides in regulation of energy homeostasis of the organism and their role as markers of metabolic disorders in obesity (Ob) in animal experimental models and in clinical observations is reviewed. The energy homeostasis of the body is controlled via competition of alternative regulatory mechanisms that are mainly localized in the hypothalamus (HT). At the level of aminergic regulation, these are the serotonin and dopamine systems; at the level of the peptidergic system, these are NPY/AgRP and POMC/CART-related peptides. Opioid and cannabinoid receptors and their endogenous ligands closely linked to peptidergic and aminergic regulatory subsystems of the central nervous system ensure the connection between the «metabolic» regulation loop responding to a deficit or excess of energy substrates the «hedonistic» one associated with the body’s perception of pleasure from food consumption. The response of peptidergic and aminergic HT neurons to food and hormonal signals originating from the outside is based on the interaction between the corresponding ligands and G-protein-coupled receptors specific to them. Disruption or breakdown of the central mechanisms is considered to be one of the main pathogenetic factors of obesity and, simultaneously, the reason why reducing diet therapy proves inefficient or unstable. Partial permeability of the blood—brain barrier for neuropeptides makes them an attractive biomarker in the diagnosis of metabolic abnormalities in obese patients.

Oxidative Stress Inhibits Healthy Adipose Expansion Through Suppression of SREBF1-Mediated Lipogenic Pathway.

Recent studies have emphasized the association of adipose oxidative stress (Fat reactive oxygen species [ROS]) with the pathogenesis of metabolic disorders in obesity. However, the causal roles of Fat ROS in metabolic disturbances in vivo remain unclear because no mouse model has been available in which oxidative stress is manipulated by targeting adipocytes. In this research, we generated two models of Fat ROS-manipulated mice and evaluated the metabolic features in diet-induced obesity. Fat ROS-eliminated mice, in which Cat and Sod1 were overexpressed in adipocytes, exhibited adipose expansion with decreased ectopic lipid accumulation and improved insulin sensitivity. Conversely, Fat ROS-augmented mice, in which glutathione was depleted specifically in adipocytes, exhibited restricted adipose expansion associated with increased ectopic lipid accumulation and deteriorated insulin sensitivity. In the white adipose tissues of these mice, macrophage polarization, tissue fibrosis, and de novo lipogenesis were significantly changed. In vitro approaches identified KDM1A-mediated attenuation of sterol-regulatory element-binding transcription factor 1 (SREBF1) transcriptional activities as the underlying mechanism for the suppression of de novo lipogenesis by oxidative stress. Thus, our study uncovered the novel roles of Fat ROS in healthy adipose expansion, ectopic lipid accumulation, and insulin resistance, providing the possibility for the adipocyte-targeting antioxidant therapy.

P2096The pathological role of coagulation factors in promoting brown adipose tissue dysfunction and systemic metabolic disorder in obesity

P2096The pathological role of coagulation factors in promoting brown adipose tissue dysfunction and systemic metabolic disorder in obesity

Sodium Butyrate Protects -Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice.

Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in Type II diabetes and obesity remains unknown. Here, we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively. Glucose intolerance, metabolic parameters, cardiac function, and remodeling were assessed. Histological analysis and cellular signaling were examined at 24 weeks following euthanization of mice. HFD-fed mice demonstrated myocardial dysfunction and profound interstitial fibrosis, which were attenuated by HDAC inhibition. HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations, and cardiac hypertrophy, these effects were prevented by HDAC inhibition. Furthermore, HDAC inhibition attenuated myocyte apoptosis, reduced production of reactive oxygen species, and increased angiogenesis in the HFD-fed myocardium. Notably, HFD induced decreases in MKK3, p38, p38 regulated/activated protein kinase (PRAK), and Akt-1, but not p44/42 phosphorylation, which were prevented by HDAC inhibition. These results suggest that HDAC inhibition plays a critical role to preserve cardiac performance and mitigate metabolic disorders in obesity and diabetes, which is associated with MKK3/p38/PRAK pathway. The study holds promise in developing a new therapeutic strategy in the treatment of Type II diabetic-induced heart failure and metabolic disorders. J. Cell. Biochem. 118: 2395-2408, 2017. © 2017 Wiley Periodicals, Inc.

Functional Plasticity of Adipose-Derived Stromal Cells During Development of Obesity.

Obesity is a major risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Expansion of the adipose mass requires adipocyte precursor cells that originate from multipotent adipose-derived stromal cells (ASCs), which in turn also participate in repair activities. ASC function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity. We tested the hypothesis that microenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. Domestic pigs were fed with an atherogenic (n = 7) or normal (n = 7) diet for 16 weeks. Abdominal adipose tissue biopsies were collected after 8, 12, and 16 weeks of diet for ASC isolation and immunohistochemistry of in situ ASCs and tumor necrosis factor-α (TNF-α). Longitudinal changes in proliferation, differentiation, and anti-inflammatory functions of ASCs were assessed. At 16 weeks, upregulated TNF-α expression in adipose tissue from obese pigs was accompanied by increased numbers of adipocyte progenitors (CD24(+)/CD34(+)) in adipose tissue and enlarged adipocyte size. In vitro, ASCs from obese pigs showed enhanced adipogenic and osteogenic propensity, which was abolished by anti-TNF-α treatment, whereas lean ASCs treated with TNF-α showed enhanced adipogenesis. Furthermore, obese ASCs showed increased senescence compared with lean ASCs, whereas their immunomodulatory capacity was preserved. Adipose tissue inflammation promotes an increase in resident adipocyte progenitors and upregulated TNF-α enhances ASC adipogenesis. Thus, adipose tissue anti-inflammatory strategies might be a novel target to attenuate obesity and its complications. Adipose-derived stromal cell (ASC) function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity. This study tested the hypothesis that microenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. It was found that ASCs show increased propensity for differentiation into adipocytes, which is partly mediated by upregulated tumor necrosis factor-α (TNF-α), likely in their adipose tissue microenvironment. Furthermore, TNF-α magnified obese ASC senescence, although it did not regulate their anti-inflammatory properties. Thus, adipose tissue inflammation might be a novel therapeutic target to avert ASC maldifferentiation and senescence.

Gpr97 is dispensable for metabolic syndrome but is involved in macrophage inflammation in high-fat diet-induced obesity in mice.

Local inflammation in tissues is one of primary causes in development of metabolic disorder in obesity. The accumulation of macrophages in some tissues can induce inflammatory reactions in obesity. Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly. In our research, we investigated Gpr97 in regulating macrophage inflammation and metabolic dysfunction in the high-fat diet (HFD)-induced obese mice. The major metabolic phenotyping were not different after Gpr97 knockout in HFD-fed mice. Similar pathological alterations in adipose tissue, liver, and kidney were observed in Gpr97−/− HFD mice compared with WT-HFD mice. In white adipose tissue, loss of Gpr97 reduced the ratio of M1-macrophages and increased the M2-macrophage ratio, which was opposite to that seen in the wild-type HFD mice. More macrophages invaded in the liver and kidney after Gpr97 knockout in HFD mice. Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97−/− HFD mice compared to those in wild-type HFD mice. The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity.

Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action?

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale “omics” studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

Targeting Phosphodiesterase 4 to Block the Link between Acute Exacerbation of Chronic Obstructive Pulmonary Disease and the Metabolic Complications

The metabolic disorders such as obesity and diabetes are found to be more frequent in chronic obstructive pulmonary disease (COPD). The chronic systemic inflammation orchestrated by macrophages constitutes one critical pathophysiological process underlying both acute exacerbation of COPD (AECOPD) and its metabolic complications such as obesity and diabetes. The cyclic adenosine monophosphate (cAMP) signaling controlled by phosphodiesterase (PDE) 4 is a pivotal intracellular modulator for macrophages functions in immune inflammatory response underlying AECOPD as well as obesity and diabetes. Targeting PDE4/cAMP signaling has been suggested to be effective in treating AECOPD or the metabolic disorders of obesity and diabetes. It is therefore reasonable to hypothesize that the chronic systemic inflammation can be a critical link between AECOPD and the metabolic disorders and targeting the PDE4/cAMP signaling can be effective to block this link between AECOPD and the associated metabolic complications.

Effects of bariatric surgery on the level of hormones that regulate body weight. What is the basis of success?

The growth of obesity and type 2 diabetes incidence has made bariatric surgery a widespread method of treatment. The effectiveness of bariatricoperations in the treatment of obesity and related metabolic diseases is thoroughly highlighted in medical literature. However, the resultsof surgery do not always correlate with type of operation. As before, the mechanisms have not been fully studied of how the bariatric surgeryinfluence on insulinresistance, entero-insulin axes, adipokines. Understanding such mechanisms will allow us to determine more precisely theindications relating to surgical treatment, and enhance the effectiveness of surgery in specific patient. The review is focusing on the influence ofvarious types of bariatric surgery on the level of adipokines and incretines that participate in regulation of appetite and of fat and carbohydratemetabolism. The article elaborates modern concepts related to the impact of bariatric operations on metabolic disorders in obesity.

MicroRNA-149 inhibits PARP-2 and promotes mitochondrial biogenesis via SIRT-1/PGC-1α network in skeletal muscle.

High-fat diet (HFD) plays a central role in the initiation of mitochondrial dysfunction that significantly contributes to skeletal muscle metabolic disorders in obesity. However, the mechanism by which HFD weakens skeletal muscle metabolism by altering mitochondrial function and biogenesis is unknown. Given the emerging roles of microRNAs (miRNAs) in the regulation of skeletal muscle metabolism, we sought to determine whether activation of a specific miRNA pathway would rescue the HFD-induced mitochondrial dysfunction via the sirtuin-1 (SIRT-1)/ peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, a pathway that governs genes necessary for mitochondrial function. We here report that miR-149 strongly controls SIRT-1 expression and activity. Interestingly, miR-149 inhibits poly(ADP-ribose) polymerase-2 (PARP-2) and so increased cellular NAD(+) levels and SIRT-1 activity that subsequently increases mitochondrial function and biogenesis via PGC-1α activation. In addition, skeletal muscles from HFD-fed obese mice exhibit low levels of miR-149 and high levels of PARP-2, and they show reduced mitochondrial function and biogenesis due to a decreased activation of the SIRT-1/PGC-1α pathway, suggesting that mitochondrial dysfunction in the skeletal muscle of obese mice may be because of, at least in part, miR-149 dysregulation. Overall, miR-149 may be therapeutically useful for treating HFD-induced skeletal muscle metabolic disorders in such pathophysiological conditions as obesity and type 2 diabetes.

Mineralocorticoid receptor throughout the vessel: a key to vascular dysfunction in obesity

This editorial refers to ‘Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity’[†][1], by N. Schafer et al. , on page 3515 Obesity is a highly prevalent chronic condition and a major risk factor for several metabolic and cardiovascular (CV) diseases. Numerous human studies have demonstrated that obesity is associated with hypertension and vascular dysfunction secondary to arterial stiffness, reduced endothelium-dependent relaxation, and atherosclerosis.1 The exact mechanisms implicated in obesity-related vascular dysfunction have not been fully elucidated, but are likely to involve a complex interplay between multiple endocrine and paracrine factors, inflammation, oxidative stress, and structural modifications of the vessel. In recent years there has been a growing interest in the simultaneous worldwide increase in the prevalence of obesity, hypertension, and hyperaldosteronism, and a possible inter-relationship between these conditions. The relevance of aldosterone to human health is supported by prospective studies demonstrating a positive correlation between plasma levels of aldosterone and CV mortality.2 Further, pivotal clinical trials have shown that mineralocorticoid receptor (MR) antagonists, such as spironolactone or eplerenone, markedly improve morbidity and mortality in heart failure.3 We and others have shown that obesity is associated with increased aldosterone production in humans and increased aldosterone and MR levels in obese diabetic mice.4,5 MR blockade improved the proinflammatory cytokine profiles of adipose tissue in the obese mice. These findings led to the hypothesis that elevated aldosterone levels contribute to CV injury, progression of atherosclerosis, and metabolic disorders in obesity ( Figure 1 ). The specific mechanisms for CV injury may be related to aldosterone's renal effects to promote sodium retention and volume expansion as well as to MR activation in multiple extrarenal tissues, including the heart, vasculature, monocytes/macrophages, and adipose tissue. Specifically in vessels, aldosterone and/or MR activation increases vascular macrophage infiltration, enhances the proinflammatory cytokine profile, … [1]: #fn-2

Obesity-metabolic derangement preserves hemodynamics but promotes intrarenal adiposity and macrophage infiltration in swine renovascular disease

Obesity-metabolic disorders (ObM) often accompany renal artery stenosis (RAS). We hypothesized that the coexistence of ObM and RAS magnifies inflammation and microvascular remodeling in the stenotic kidney (STK) and aggravates renal scarring. Twenty-eight obesity-prone Ossabaw pigs were studied after 16 wk of a high-fat/high-fructose diet or standard chow including ObM-sham, ObM-RAS, Lean-RAS, or Lean-sham (normal control) groups. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by multidetector computed tomography (CT), renal oxygenation and tubular transport capability by blood-oxygen-level-dependent MRI, and microcirculation by micro-CT for vessel density, and Western blotting for protein expressions of angiogenic factors (VEGF/FLK-1). Renal vein and inferior vena cava levels of inflammatory cytokines were measured to evaluate systemic and kidney inflammation. Macrophage (MØ) infiltration and subpopulations, fat deposition in the kidney, and inflammation in perirenal and abdominal fat were also examined. GFR and RBF were decreased in Lean-STK but relatively preserved in ObM-STK. However, ObM-STK showed impaired tubular transport function, suppressed microcirculation, and stimulated glomerulosclerosis. ObM diet interacted with RAS to blunt angiogenesis in the STK, facilitated the release of inflammatory cytokines, and led to greater oxidative stress than Lean-STK. The ObM diet also induced fat deposition in the kidney and infiltration of proinflammatory M1-MØ, as also in perirenal and abdominal fat. Coexistence of ObM and RAS amplifies renal inflammation, aggravates microvascular remodeling, and accelerates glomerulosclerosis. Increased adiposity and MØ-accentuated inflammation induced by an ObM diet may contribute to structural injury in the post-STK kidney.

Glycine metabolism in animals and humans: implications for nutrition and health

Glycine is a major amino acid in mammals and other animals. It is synthesized from serine, threonine, choline, and hydroxyproline via inter-organ metabolism involving primarily the liver and kidneys. Under normal feeding conditions, glycine is not adequately synthesized in birds or in other animals, particularly in a diseased state. Glycine degradation occurs through three pathways: the glycine cleavage system (GCS), serine hydroxymethyltransferase, and conversion to glyoxylate by peroxisomal D-amino acid oxidase. Among these pathways, GCS is the major enzyme to initiate glycine degradation to form ammonia and CO2 in animals. In addition, glycine is utilized for the biosynthesis of glutathione, heme, creatine, nucleic acids, and uric acid. Furthermore, glycine is a significant component of bile acids secreted into the lumen of the small intestine that is necessary for the digestion of dietary fat and the absorption of long-chain fatty acids. Glycine plays an important role in metabolic regulation, anti-oxidative reactions, and neurological function. Thus, this nutrient has been used to: (1) prevent tissue injury; (2) enhance anti-oxidative capacity; (3) promote protein synthesis and wound healing; (4) improve immunity; and (5) treat metabolic disorders in obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, cancers, and various inflammatory diseases. These multiple beneficial effects of glycine, coupled with its insufficient de novo synthesis, support the notion that it is a conditionally essential and also a functional amino acid for mammals (including pigs and humans).

Dynamic Analysis of the Possible Effects of Leptin in Some Metabolic Disorders in Obesity

Obesity and metabolic syndrome represent an increasing epidemiological challenge for society given the associated social and health implications. Obesity is related to different metabolic disorders, like diabetes mellitus type 2, which has been subject to study in the last decades. Nowadays, most of the related research focuses on endocrine aspects, especially related to adipose tissue. This is due to the fact that some adipocytokines are proven to be of great relevance as therapeutic agents both for obesity and mellitus type 2 diabetes. This work integrates some aspects of the knowledge generated under these research studies. In this context, it is proposed the design and development of a computational model that provides a better dynamic view of the existing interactions between endocrine aspects of the adipose tissue and glucose control mechanisms in people with obesity. The model behaves as an observer that estimates the dynamics of internal state variables, not easy to be measured in the clinical practice, and which helps to understand the dynamic behaviour of measurable variables. The work analyses the effects of the external energy intake and exercises over the obesity control and glycemia. The model has been validated by using other authors’ data. Predictions of the influence over the measurable variables of the behaviours considered when the virtual patient follows different diets and physical exercise are shown as results.

Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders

Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders

Genetic induction of phosphate toxicity significantly reduces the survival of hypercholesterolemic obese mice

Objective The adverse effects of metabolic disorders in obesity have been extensively studied; however, the pathologic effects of hyperphosphatemia or phosphate toxicity in obesity have not been studied in similar depth and detail, chiefly because such an association is thought to be uncommon. Studies have established that the incidence of obesity-associated nephropathy is increasing. Because hyperphosphatemia is a major consequence of renal impairment, this study determines the in vivo effects of hyperphosphatemia in obesity. Methods and results We genetically induced hyperphosphatemia in leptin-deficient obese ( ob/ ob) mice by generating ob/ ob and klotho double knockout [ ob/ ob- klotho −/−] mice. As a control, we made ob/ ob mice with hypophosphatemia by generating ob/ ob and 1- alpha hydroxylase double knockout [ ob/ ob-1 α( OH) ase −/−] mice. Compared to the wild-type mice, all three obese background mice, namely ob/ ob, ob/ ob- klotho −/−, and ob/ ob-1 α( OH) ase −/− mice developed hypercholesterolemia. In addition, the hyperphosphatemic, ob/ ob- klotho −/− genetic background induced generalized tissue atrophy and widespread soft-tissue and vascular calcifications, which led to a shorter lifespan; no such changes were observed in the hypophosphatemic, ob/ ob-1 α( OH) ase −/− mice. Significantly, in contrast to the reduced survival of the ob/ ob- klotho −/− mice, lowering serum phosphate levels in ob/ ob-1 α( OH) ase −/− mice showed no such compromised survival, despite both mice being hypercholesterolemic. Conclusion These genetic manipulation studies suggest phosphate toxicity is an important risk factor in obesity that can adversely affect survival.