Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat

Cooney, Greg; Curi, Rui; Mitchelson, Andrew; Newsholme, Philip; Simpson, M.; Newsholme, Eric A.

doi:10.1016/s0006-291x(86)80551-4

Cited by 27 publications

(24 citation statements)

References 15 publications

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“…ISA analysis indicated that both Glc and Gln make substantial contributions of carbon for lipogenesis under all conditions examined. AcAc (10 mM) was readily converted to lipid, indicating that these cell lines have a large capacity for AcAc utilization, consistent with the results in animal studies (9,10). The activity of acetoacetyl-CoA syn- Amounts of total fatty acids under three culture conditions on day 6 measured by GC-MS using triheptadecanoin as the internal standard (conditions are as described in Materials and Methods and Fig.…”

Section: Lipogenesis Under Varied Conditions For Differentiation: Addsupporting

confidence: 81%

“…In addition, incorporation of ␤ -hydroxybutyrate into fatty acid was increased in brown adipose tissue of cold-adapted rats (8). In concert with these fluxes, increased levels of mitochondrial enzymes required for the conversions of AcAc to acetyl CoA, 3-oxoacid CoA transferase, and acetoacetyl-CoA thiolase have been found in brown adipose tissue from suckling and weanling rats (9,10). In addition to fatty acid synthesis, nutrients are required for the glycerol backbone of the triglyceride.…”

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confidence: 99%

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Quantifying carbon sources for de novo lipogenesis in wild-type and IRS-1 knockout brown adipocytes

Yoo

Stephanopoulos

Kelleher

2004

Journal of Lipid Research

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Studies were conducted to evaluate the flux of various carbon sources to lipogenesis during brown adipocyte differentiation. 13 C labeling and isotopomer spectral analysis quantified the contribution of metabolites to de novo lipogenesis in wild-type (WT) and insulin receptor substrate-1 knockout (KO) brown adipocytes. Both glucose (Glc) and glutamine (Gln) provided substantial fractions of the lipogenic acetyl CoA for both WT and KO cells in standard media, together contributing 60%. Adding acetoacetate (AcAc; 10 mM) to the medium resulted in a large flux of AcAc to lipid, representing 70% of the lipogenic acetyl CoA and decreasing the contribution of Glc plus Gln to 30%. For WT cells, the fractional synthesis of new fatty acids during 4 days of differentiation was 80% of the total. Similarly, 80% of the lipidic glycerol was derived from Glc in the medium; Gln was not a precursor for glycerol. When Gln was removed from the medium, the contribution of Glc to fatty acid synthesis doubled, replacing most of the contribution of Gln and maintaining total lipogenesis. Conversely, removal of Glc dramatically decreased lipogenesis. These results indicate that Glc's distinct role in lipid synthesis during differentiation cannot be replaced by other carbon sources, consistent with the role of Glc supplying NADPH and/or glycerol for triglyceride synthesis. The differentiation of brown adipocyte cells from a fibroblast-like precursor is evolutionarily related to prehibernation fat accumulation and thus linked to total body energy metabolism (1). Adipogenesis occurs under conditions of excess nutrients and accompanying hormones and involves changes in gene expression and cell signaling, leading to a substantial increase in de novo synthesis and storage of triglyceride. Cell surface receptors, especially for insulin and insulin-like growth factor-1, provide a mechanism for hormonal response to nutrient abundance. Recent investigations of adipogenesis have focused on gene expression and cell signaling events associated with this conversion (2-4). The importance of the insulin receptor substrate-1 (IRS-1) signaling pathway for differentiation has been demonstrated by the finding that an IRS-1 knockout (KO) preadipocyte cell line is unable to differentiate under the standard condition in which wildtype (WT) cells accumulate triglyceride and express adipocyte-specific genes, including UCP-1 and fatty acid synthase (5). A consequence of the IRS-1 KO is that these cells are deficient in insulin-stimulated glucose (Glc) uptake via the Glc transporter GLUT4. The studies of in vitro adipogenesis are normally conducted under constant nutrient conditions using cell culture media in which Glc (25 mM) and glutamine (Gln; 2-4 mM) provide the major carbon sources for cell metabolism. In the work presented here, we investigate the role of the nutrient and hormonal environment on the process of lipogenesis accompanying brown adipocyte differentiation.Animal studies support the concept that Glc is a major carbon source for brown adip...

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Section: Lipogenesis Under Varied Conditions For Differentiation: Addsupporting

confidence: 81%

mentioning

confidence: 99%

Quantifying carbon sources for de novo lipogenesis in wild-type and IRS-1 knockout brown adipocytes

Yoo

Stephanopoulos

Kelleher

2004

Journal of Lipid Research

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“…However, the ability to take up glutamine stresses the similarities with intestine, an organ that takes up glutamine, releases alanine and produces free NH4' (Brosnan et al, 1983;Windmueller & Spaeth, 1974), which is later detoxified by the liver. No data are available as -to the possible production of free NH4+ by the IBAT, but the net positive amino acid nitrogen balances observed seem to suggest the possible release of NH4+ by the IBAT, which contains active glutaminase (Cooney et al, 1986) and adenylate deaminase (Lopez-Soriano & Alemany, 1986). NH4+ is itselfa powerful signal to control glycolysis (Abrahams & Younathan, 1971) and Na+-K+ ATPases (Robinson, 1970).…”

Section: Discussionmentioning

confidence: 99%

Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation

López‐Soriano

López

Mampel

et al. 1988

Biochemical Journal

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The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine-and proline efflux-that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids.

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“…21,22 The spleen and thymus were homogenized using a Polytron (PCU-2) in a proportion of 1 : 10 with extraction buer. Lymphocytes were disrupted in extraction buer using a Sonicator (Thornton) as previously described.…”

Section: Enzyme Assaysmentioning

confidence: 99%

Effect of dietary fat on lymphocyte proliferation and metabolism

Otton

Graziola

Souza

et al. 1998

Cell Biochemistry & Function

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The effect of diets enriched with fat containing different fatty acids on glucose and glutamine metabolism of mesenteric lymph nodes lymphocytes, spleen, and thymus and lymphocyte proliferation was examined. The following fat-rich diets were tested: (1) standard chow (CC); (2) medium chain saturated fatty acids (MS)--coconut fat oil; (3) long chain saturated fatty acids (LS)--cocoa butter; (4) monounsaturated fatty acids (MU)--canola oil (n-9); (5) polyunsaturated fatty acids (PU)--soybean oil (n-6). Of the fat-rich diets tested, MS was the one to present the least pronounced effect. Lymphocyte proliferation was reduced by LS (64 per cent), MU (55 per cent), and PU (60 per cent). Hexokinase activity was enhanced in lymph node lymphocytes by PU (67 per cent), in the spleen by MS (42 per cent), and in the thymus by PU (30 per cent). This enzyme activity was reduced in the spleen (33 per cent) by LS and MU (35 per cent). In the thymus, this enzyme activity was reduced by LS (26 per cent) and MU (13 per cent). Maximal phosphate-dependent glutaminase activity was raised in lymphocytes by MS (70 per cent) and MU (20 per cent). This enzyme activity, however, was decreased in lymphocytes by PU (26 per cent), in the spleen by LS (15 per cent), and in the thymus by MU (44 per cent). Citrate synthase activity was increased in lymphocytes by MU (35 per cent), in the spleen by LS (56 per cent) and MU (68 per cent), and in the thymus by LS (42 per cent). This enzyme activity was decreased in lymphocytes by PU (24 per cent) only. [U-14C]-Glucose decarboxylation was raised by all fat-rich diets; MS (88 per cent). LS (39 per cent), MU (33 per cent), and PU (50 per cent), whereas [U-14C]-glutamine decarboxylation was increased by LS (53 per cent) and MU (55 per cent) and decreased by MS (17 per cent). The results presented indicate that the reduction in lymphocyte proliferation due to LS, LU and PU could well be a consequence of changes in glucose and glutamine metabolism.

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Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat

Cited by 27 publications

References 15 publications

Quantifying carbon sources for de novo lipogenesis in wild-type and IRS-1 knockout brown adipocytes

Quantifying carbon sources for de novo lipogenesis in wild-type and IRS-1 knockout brown adipocytes

Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation

Effect of dietary fat on lymphocyte proliferation and metabolism

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