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Research paper thumbnail of The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

Journal of Nephrology, 2020

Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns... more Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available...

Research paper thumbnail of Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes

Journal of lipid research, 2017

Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogen... more Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis, and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown. Here, we find that in primary brown adipocytes and brown adipocyte-derived cell line (IMBAT-1), acute inhibition and longer-term knockdown of DGAT2 links the increased de novo synthesis of fatty acids from glucose to a pool of TAG that is simultaneously hydrolyzed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesize a functionally distinct pool of TAG to which DGAT2 also contributes. The DGAT2-dependent channelling of (14)C from glucose into TAG and CO2 was reproduced in β3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of UCP1 and genes important in FA activatio...

Research paper thumbnail of Hepatic VLDL secretion: DGAT1 determines particle size but not particle number which is supported by DGAT2 activity in the absence of DGAT1

Journal of Lipid Research

Research paper thumbnail of Hepatic triacylglycerol synthesis and secretion: DGAT2 as the link between glycaemia and triglyceridaemia

Biochemical Journal, 2013

The liver regulates both glycaemia and triglyceridaemia. Hyperglycaemia and hypertriglyceridaemia... more The liver regulates both glycaemia and triglyceridaemia. Hyperglycaemia and hypertriglyceridaemia are both characteristic of (pre)diabetes. Recent observations on the specialised role of DGAT2 (diacylglycerol acyltransferase 2) in catalysing the de novo synthesis of triacylglycerols from newly synthesized fatty acids and nascent diacylglycerols identifies this enzyme as the link between the two. This places DGAT2 at the centre of carbohydrate-induced hypertriglyceridaemia and hepatic steatosis. This function is complemented, but not substituted for, by the ability of DGAT1 to rescue partial glycerides from complete hydrolysis. In peripheral tissues not normally considered to be lipogenic, synthesis of triacylgycerols may largely bypass DGAT2 except in hyperglycaemic/hyperinsulinaemic conditions, when induction of de novo fatty acid synthesis in these tissues may contribute towards increased triacylglycerol secretion (intestine) or insulin resistance (adipose tissue, and cardiac and ...

Research paper thumbnail of Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis

Trends in Endocrinology & Metabolism

Research paper thumbnail of The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis

Journal of Nephrology, 2020

Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns... more Peritoneal dialysis (PD) is a viable but under-prescribed treatment for uremic patients. Concerns about its use include the bio-incompatibility of PD fluids, due to their potential for altering the functional and anatomical integrity of the peritoneal membrane. Many of these effects are thought to be due to the high glucose content of these solutions, with attendant issues of products generated during heat treatment of glucose-containing solutions. Moreover, excessive intraperitoneal absorption of glucose from the dialysate has many potential systemic metabolic effects. This article reviews the efforts to develop alternative PD solutions that obviate some of these side effects, through the replacement of part of their glucose content with other osmolytes which are at least as efficient in removing fluids as glucose, but less impactful on patient metabolism. In particular, we will summarize clinical studies on the use of alternative osmotic ingredients that are commercially available...

Research paper thumbnail of Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes

Journal of lipid research, 2017

Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogen... more Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis, and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown. Here, we find that in primary brown adipocytes and brown adipocyte-derived cell line (IMBAT-1), acute inhibition and longer-term knockdown of DGAT2 links the increased de novo synthesis of fatty acids from glucose to a pool of TAG that is simultaneously hydrolyzed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesize a functionally distinct pool of TAG to which DGAT2 also contributes. The DGAT2-dependent channelling of (14)C from glucose into TAG and CO2 was reproduced in β3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of UCP1 and genes important in FA activatio...

Research paper thumbnail of Hepatic VLDL secretion: DGAT1 determines particle size but not particle number which is supported by DGAT2 activity in the absence of DGAT1

Journal of Lipid Research

Research paper thumbnail of Hepatic triacylglycerol synthesis and secretion: DGAT2 as the link between glycaemia and triglyceridaemia

Biochemical Journal, 2013

The liver regulates both glycaemia and triglyceridaemia. Hyperglycaemia and hypertriglyceridaemia... more The liver regulates both glycaemia and triglyceridaemia. Hyperglycaemia and hypertriglyceridaemia are both characteristic of (pre)diabetes. Recent observations on the specialised role of DGAT2 (diacylglycerol acyltransferase 2) in catalysing the de novo synthesis of triacylglycerols from newly synthesized fatty acids and nascent diacylglycerols identifies this enzyme as the link between the two. This places DGAT2 at the centre of carbohydrate-induced hypertriglyceridaemia and hepatic steatosis. This function is complemented, but not substituted for, by the ability of DGAT1 to rescue partial glycerides from complete hydrolysis. In peripheral tissues not normally considered to be lipogenic, synthesis of triacylgycerols may largely bypass DGAT2 except in hyperglycaemic/hyperinsulinaemic conditions, when induction of de novo fatty acid synthesis in these tissues may contribute towards increased triacylglycerol secretion (intestine) or insulin resistance (adipose tissue, and cardiac and ...

Research paper thumbnail of Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis

Trends in Endocrinology & Metabolism

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