Protein Kinase C Is Activated and Diacylglycerol Is Elevated in Epidermal Cells from Sencar Mice Fed High Fat Diets

Choe, Myeon; Kris, Edward S.; Luthra, Rajesh; Copenhaver, James; Pelling, Jill C.; Donnelly, Thomas E.; Birt, Diane F.

doi:10.1093/jn/122.12.2322

Cited by 31 publications

(7 citation statements)

References 15 publications

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“…In a state of energy excess, intracellular long-chain fatty acyl-CoA (LC-CoA) and triglycerides accumulate (41). An accumulation of LC-CoA could also increase the concentration of diacylglycerol (DAG), an activator of protein kinase C (PKC) (44). Elevated malonyl-CoA inhibits carnitine palmitoyltransferase I, which is necessary for the transfer of fatty acids as LC-CoA through the mitochondrial membrane for oxidation and is thought to act as an intracellular signal of fuel availability.…”

Section: Mechanisms Involved In the Development Of Insulin Resistancementioning

confidence: 99%

Mechanisms Linking Diet and Colorectal Cancer: The Possible Role of Insulin Resistance

Bruce¹,

Wolever²,

Giacca³

2000

Nutrition and Cancer

147

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Diet is clearly implicated in the origin of colorectal cancer, with risk factors for the disease including reduced consumption of vegetables, fiber, and starch and increased consumption of red meat and animal fat. Several hypotheses have been developed to explain these associations. Most recently, McKeown-Eyssen and Giovannucci noted the similarity of the risk factors for colorectal cancer and those for insulin resistance and suggested that insulin resistance leads to colorectal cancer through the growth-promoting effect of elevated levels of insulin, glucose, or triglycerides. We briefly review the evidence from observational, epidemiological, and experimental animal studies linking diet with insulin resistance and colorectal cancer. The evidence suggests that diets high in energy and saturated fat and with high glycemic index carbohydrate and low levels of fiber and n-3 fatty acids lead to insulin resistance with hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. We then consider how insulin, the related insulin-like growth factors, triglycerides, and nonesterified fatty acids could lead to increased growth of colon cancer precursor lesions and the development of colorectal cancer. Finally, we consider the implications of this scheme on possible future research directions, including studies of satiety and clinical tests of the importance of insulin resistance in the colon carcinogenesis process.

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Section: Mechanisms Involved In the Development Of Insulin Resistancementioning

confidence: 99%

Mechanisms Linking Diet and Colorectal Cancer: The Possible Role of Insulin Resistance

Bruce¹,

Wolever²,

Giacca³

2000

Nutrition and Cancer

147

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“…They proposed that bacteria expressing phospholipase C would be capable of such a conversion and that this was dependent upon the presence of secondary bile acids. Several studies have shown that a high-fat diet results in increased fecal concentrations of DAG (7,35,39). The interaction of DAG with PKC is thought to be stereospecific and stimulated only by DAG with a 1,2-sn configuration (33).…”

mentioning

confidence: 99%

Microbial Species Involved in Production of 1,2- sn -Diacylglycerol and Effects of Phosphatidylcholine on Human Fecal Microbiota

Vulevic

McCartney

Gee

et al. 2004

Appl Environ Microbiol

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1,2-sn-Diacylglycerols (DAGs) are activators of protein kinase C (PKC), which is involved in the regulation of colonic mucosal proliferation. Extracellular DAG has been shown to stimulate the growth of cancer cell lines in vitro and may therefore play an important role in tumor promotion. DAG has been detected in human fecal extracts and is thought to be of microbial origin. Hitherto, no attempts have been made to identify the predominant fecal bacterial species involved in its production. We therefore used anaerobic batch culture systems to determine whether fecal bacteria could utilize phosphatidylcholine (0.5% [wt/vol]) to produce DAG. Production was found to be dependent upon the presence of the substrate and was enhanced in the presence of high concentrations of deoxycholate (5 and 10 mM) in the growth medium. Moreover, its production increased with the pH, and large inter-and intraindividual variations were observed between cultures seeded with inocula from different individuals. Clostridia and Escherichia coli multiplied in the fermentation systems, indicating their involvement in phosphatidylcholine metabolism. On the other hand, there was a significant decrease in the number of Bifidobacterium spp. in the presence of phosphatidylcholine. Pure-culture experiments showed that 10 of the 12 strains yielding the highest DAG levels (>50 nmol/ml) were isolated from batch culture enrichments run at pH 8.5. We found that the strains capable of producing large amounts of DAG were predominantly Clostridium bifermentans (8 of 12), followed by Escherichia coli (2 of 12). Interestingly, one DAG-producing strain was Bifidobacterium infantis, which is often considered a beneficial gut microorganism. Our results have provided further evidence that fecal bacteria can produce DAG and that specific bacterial groups are involved in this process. Future strategies to reduce DAG formation in the gut should target these species.

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“…In Sencar mice fed 24.5% corn oil diets for six to seven weeks, PKC activity was elevated compared with a 5% corn oil diet in the particulate fraction from mice fed the high corn oil diet (17). However, in studies in which Sencar mice were prefed for 13 weeks agar-containing control and highfat diets with energy from fat and carbohydrate balanced, particulate PKC activity was lower in mice fed the high-fat diet than in control mice (18).…”

Section: Introductionmentioning

confidence: 93%

Dietary lipid varying in corn and coconut oil influences protein Kinase C in phorbol ester‐treated mouse skin

Mouat

Locniskar²

1998

Nutrition and Cancer

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An earlier study indicated that increased levels of corn oil in the diet resulted in decreased tumor yield after promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate in Sencar mouse epidermis (J Leyton, ML Lee, M Locniskar, MA Belury, TJ Slaga, et al. Cancer Res 51, 907-915, 1991). In the present study we investigated whether corn oil diets could alter the subcellular distribution and activity of protein kinase C (PKC), which is part of an important signaling pathway in carcinogenesis. We used three 15% (wt/wt) fat semipurified diets containing three ratios of corn oil to coconut oil: 1.0%:14.0% (Diet L), 7.9%:7.1% (Diet M), and 15.0%:0.0% (Diet H). The translocation to the membrane fraction of epidermal PKC by 12-O-tetradecanoylphorbol-13-acetate was decreased as the corn oil content of the diet was increased, and this correlates with the decrease in tumor yield. The translocation to the membrane fraction of specific isoforms of PKC was affected by increased dietary corn oil: the largest decreases were in cytosolic PKC-alpha and -beta, and the smallest change was in PKC-epsilon. The other isoforms, PKC-delta and -zeta, were unaffected. The major constituent of corn oil is linoleic acid, which did not affect the binding of phorbol ester to PKC, which suggests that inhibition of such binding was not responsible for the effects of increased dietary corn oil. Products of linoleic acid metabolism, i.e., arachidonic acid and 13-hydroxyoctadecadienoic acid, also did not affect the binding of phorbol ester to PKC. Thus the results of these studies suggest that the subcellular distributions of PKC and its isoforms can be modulated by dietary lipids.

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Protein Kinase C Is Activated and Diacylglycerol Is Elevated in Epidermal Cells from Sencar Mice Fed High Fat Diets

Cited by 31 publications

References 15 publications

Mechanisms Linking Diet and Colorectal Cancer: The Possible Role of Insulin Resistance

Mechanisms Linking Diet and Colorectal Cancer: The Possible Role of Insulin Resistance

Microbial Species Involved in Production of 1,2- sn -Diacylglycerol and Effects of Phosphatidylcholine on Human Fecal Microbiota

Dietary lipid varying in corn and coconut oil influences protein Kinase C in phorbol ester‐treated mouse skin

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