Angiogenesis is necessary for the growth of adipose tissue. Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism. We investigated the effect of curcumin, the major polyphenol in turmeric spice, on angiogenesis, adipogenesis, differentiation, apoptosis, and gene expression involved in lipid and energy metabolism in 3T3-L1 adipocyte in cell culture systems and on body weight gain and adiposity in mice fed a high-fat diet (22%) supplemented with 500 mg curcumin/kg diet for 12 wk. Curcumin (5-20 micromol/L) suppressed 3T3-L1 differentiation, caused apoptosis, and inhibited adipokine-induced angiogenesis of human umbilical vein endothelial cells. Supplementing the high-fat diet of mice with curcumin did not affect food intake but reduced body weight gain, adiposity, and microvessel density in adipose tissue, which coincided with reduced expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Curcumin increased 5'AMP-activated protein kinase phosphorylation, reduced glycerol-3-phosphate acyl transferase-1, and increased carnitine palmitoyltransferase-1 expression, which led to increased oxidation and decreased fatty acid esterification. The in vivo effect of curcumin on the expression of these enzymes was also confirmed by real-time RT-PCR in subcutaneous adipose tissue. In addition, curcumin significantly lowered serum cholesterol and expression of PPARgamma and CCAAT/enhancer binding protein alpha, 2 key transcription factors in adipogenesis and lipogenesis. The curcumin suppression of angiogenesis in adipose tissue together with its effect on lipid metabolism in adipocytes may contribute to lower body fat and body weight gain. Our findings suggest that dietary curcumin may have a potential benefit in preventing obesity.

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Curcumin Inhibits Adipogenesis in 3T3-L1 Adipocytes and Angiogenesis and Obesity in C57/BL Mice

Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice

Glucose homeostasis and the kidney.

https://www.cell.com/trends/biochemical-sciences/pdf/0968-0004(84)90293-7.pdf

The role of ureagenesis in pH homeostasis

According to recent experimental data the renal transport of amino acids (AA) is characterized as follows. 1.Kinetics: Several reabsorption systems remove AA from the tubular fluid by active transport with Michaelis-Menten type kinetics. Passive diffusion does play only a relatively small role in reabsorption, but determines the pump leak steady state concentration at the end of the tubule. 2.Stereospecificity: Except for aspartate the naturally occurring L-analogs show a much larger affinity to the transport “carriers” than the D-isomers do. 3.Specificity: Separate transport mechanisms exist for a) the “acidic” AA (Glu and Asp); b) the “dibasic” AA (Arg, Lys, Orn); c) cystine/cysteine; d) the “imino” acids (Pro, OH-Pro and other N-substituted AA); e) the β- and γ-AA (β-Ala, GABA, Taurine); f) all other “neutral” AA. For the group (d) and maybe also for (b) and glycine additional low capacity/high affinity systems exist. 4.Localization: Except for glycine and taurine under normal conditions more than 80% of the filtered load are reabsorbed within the first third of the proximal tubule. At an elevated load the rest of the proximal tubule (including pars recta) but not the distal nephron is included into the reabsorptive process. AA are also taken up from the peritubular blood. 5.Energy sources: At least the main part of AA uptake at the brushborder membrane is dependent from a transmembranal Na+-gradient which in turn is established by the ATP driven Na+-pumps at the basolateral side of the cell (Secondary active transport or co-transport of AA). 6.Biochemistry: The biochemical nature of the AA-“carriers” is unknown. The recent hypothesis that a “γ-glutamyl cycle” plays a major role in this context has been disproved to great extent. 7.Peptides: Oligopeptides (Angiotensin, Glutathion) filtered at the glomerulum are hydrolyzed by brushborder peptidases within the tubule lumen. The splitting products, the free constituent amino acids, are reabsorbed subsequently by their respective transport systems.

Renal transport of amino acids

. In man, HCl acidosis reduces blood and urinary urea with a concomitant rise in ammonium (NH+4) excretion. Significantly less urea is excreted following NH4Cl administration than following equimolar ingestion of NH4 HCO3. The results of these alterations in nitrogen excretion are interpreted in terms of bicarbonate utilization and production.

The effects of administrations of HCI, NH4CI and NH4HCO3 on the excretion of urea and ammonium in man

Using D-[1-14C]glucose as a tracer, renal glucose utilization and production was measured in chronic metabolic acidosis and alkalosis in dog kidney in vivo. In six experiments in acidosis, mean total renal glucose production was 4.447±1.655 SE μmol/min and glucose utilization was 4.187±0.576 SE μmol/min. In five alkalotic experiments it was found that mean total glucose production was 12.227±2.026 SE μmol/min and glucose utilization was 18.186±2.054 SE μmol/min. Renal glucose utilization and production are therefore significantly higher in alkalosis than in acidosis in vivo. Since glucose production is maximal under conditions when glutamine extraction is minimal (i.e. alkalosis), it is apparent that in alkalosis glutamine is not a major precursor of glucose.

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Glucose Utilization and Production by the Dog Kidney In Vivo in Metabolic Acidosis and Alkalosis

Enzymic method for determining the specific activity of glucose.

THE principal mechanism whereby excess hydrogen ions are excreted in man is by renal production of ammonia and subsequent urinary excretion as ammonium. The major and direct source of this renal ammoniagenesis is glutamine1. Two distinct metabolic pathways of glutamine metabolism have been demonstrated in rat, guinea-pig and dog. The intramitochondrial glutaminase I isoenzymes which hydrolyse glutamine to ammonia and glutamic acid and its subsequent deamidation to ammonia and 2-oxo-glutarate constitute the major metabolic route in the rat2. The extramitochondrial glutamine-aminotransferase-ω-amidase pathway (glutaminase II), however, has been shown to be important in the dog3. In man, whereas the glutaminase I pathway has been demonstrated4 there is no direct evidence for the latter metabolic pathway. We investigated this metabolic pathway using the alkyl substituted glutamine, L-γ-glutamylmethylamide. In contrast to glutamine, this substituted compound on deamidation yields methylamine5.

E. Bourke

Papers

The effects of administrations of HCI, NH4CI and NH4HCO3 on the excretion of urea and ammonium in man

Glucose Utilization and Production by the Dog Kidney In Vivo in Metabolic Acidosis and Alkalosis

Enzymic method for determining the specific activity of glucose.

Glutaminase II Pathway in Human Kidney

Studies on the glutamine aminotransferase-omega-amidase pathway in human kidney in vitro.