Disease relevance of LPGP1

• Similar to other lipogenic enzymes, GPAT3 may be useful as a target for the treatment of obesity [1].
• To gain more insight into the molecular mechanisms by which androgens stimulate lipogenesis and induce a marked accumulation of neutral lipids in the human prostate cancer cell line LNCaP, we studied their impact on the expression of lipogenic enzymes [2].
• Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3 [3].
• Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment [4].
• The studies also raise the possibility that the difference in the dependence of VLDL production on plasma FFAs in acute versus chronic hyperinsulinemia results from an increase in hepatic lipogenic enzymes and from the availability of an alternate substrate such as fructose [5].

Psychiatry related information on LPGP1

• Lipogenic factors (defined as either the use of steroid or alcohol abuse) were positive in 46 patients (average age, 37 years) and absent in 14 (average age, 47 years) [6].
• To test this hypothesis we investigated serum leptin levels and lipogenic enzyme activities in white adipose tissue (WAT) of male Wistar rats during 12 days of ad libitum feeding following multiple cycles of alternating food deprivation and refeeding [7].

High impact information on LPGP1

• When macrophages are stimulated with an endotoxin, they produce a factor or factors, termed cachectin, that inhibits the activity of fat-producing (lipogenic) enzymes in cultured adipocytes [8].
• The thermogenic effect of CS is small or absent in heavy smokers while the potentially atherogenic effect is maintained, and cessation of CS does not induce a rebound lipogenic milieu that specifically favors accrual of body fat in the absence of increased food intake [9].
• Precursor enrichments predicted from isotopomer ratios were close to measured SMX-acetate enrichments, indicating that SMX-acetate samples the true lipogenic acetyl-CoA pool [10].
• As a functional consequence, the lipogenic effect of SREBP2(N) in liver cells was suppressed by ATF6(N) [11].
• Phagocytosis triggered the proteolytic activation of two lipogenic transcription factors, sterol regulatory element binding protein-1a (SREBP-1a) and SREBP-2 [12].

Chemical compound and disease context of LPGP1

• Based on our previous finding that the cytotoxic effect of the flavanol epigallocatechin-3-gallate on prostate cancer cells correlates with its ability to inhibit fatty acid synthase (FAS, a key lipogenic enzyme overexpressed in many human cancers), we examined the anti-lipogenic effects of a panel of 18 naturally occurring polyphenolic compounds [13].
• Using two independent prostate cancer cell lines (LNCaP and MDA-PCa-2a), we demonstrate that coordinated stimulation of lipogenic gene expression by androgens is a common phenomenon in androgen-responsive prostate tumor lines and involves activation of the sterol regulatory element-binding protein (SREBP) pathway [14].
• First, there is the evidence that resistance to insulin-stimulated glucose metabolism is not a primary event in obesity, but is secondary to lipid accumulation resulting from full responsiveness to insulin-stimulated lipogenic activity [15].
• The down-regulation of sterol regulatory element binding protein-1c, a transcription factor controlling lipogenic gene expression, may constitute a link between thyrotoxicosis and insulin resistance [16].
• We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells [17].

Biological context of LPGP1

• Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins [2].
• This heterodimeric complex binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoter of lipogenic enzymes [18].
• Overexpression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1was identified as a candidate transcription factor responsible for lipogenic enzyme induction [19].
• Silencing of the ACC-alpha gene resulted in a similar inhibition of cell proliferation and induction of caspase-mediated apoptosis of highly lipogenic LNCaP prostate cancer cells as observed after FAS RNAi [20].
• Whereas the transcription of the glucokinase gene, for example, is stimulated by insulin without the aid of glucose, the transcriptional activation of most glycolytic and lipogenic genes in hepatocytes requires the presence of both glucose and insulin [21].

Anatomical context of LPGP1

• More specifically, it has been demonstrated that polyunsaturated fatty acid (PUFA) intake influences adipose tissue expression of leptin, and of several lipogenic enzymes and transcription factors [22].
• Transcription of the genes for lipogenic and glycolytic enzymes is stimulated by glucose in adipose tissue, liver, and pancreatic beta-cells [23].
• TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo [24].
• Overexpression of the lipogenic enzyme fatty acid synthase (FAS) is a common molecular feature in subsets of sex-steroid-related tumors including endometrium and breast carcinomas that are associated with poor prognosis [25].
• Visceral fat is characterized by its high lipogenic activity as well as its accelerated lipolytic activity [26].

Associations of LPGP1 with chemical compounds

• The mRNA of the lipogenic transcription factor, carbohydrate response element-binding protein, was undetectable in undifferentiated 3T3-L1 preadipocytes but rose dramatically during differentiation in 25 mM, but not in 5 mM, glucose [27].
• Northern blot analysis of the steady-state mRNA levels of seven different lipogenic enzymes revealed that androgens coordinately stimulate the expression of enzymes belonging to the two major lipogenic pathways: fatty acid synthesis and cholesterol synthesis [2].
• These data support the hypothesis that SREBPs are involved in the coordinate regulation of lipogenic gene expression by androgens and provide evidence for the existence of a cascade mechanism of androgen-regulated gene expression [2].
• Lipid synthesis was accompanied by increased transcription of several lipogenic proteins, including the low-density lipoprotein receptor, enzymes required for cholesterol synthesis (3-hydroxy-3-methylglutaryl CoA synthase, 3-hydroxy-3-methylglutaryl CoA reductase), and fatty acid synthase [12].
• As previous data suggested that protein kinase C plays an important role in the action of insulin and in the insulin-like effects of hGH in rat adipocytes, we tested the effects of sphingosine, a potent inhibitor of protein kinase C, on the lipogenic activity of both hormones [28].

Physical interactions of LPGP1

• Considerable differences existed between the specific activities of the fatty-acid synthase complex measured in human and rat lipogenic organs [29].

Regulatory relationships of LPGP1

• This observation led us to hypothesize that PUFA coordinately inhibit lipogenic gene transcription by suppressing the expression of SREBP-1 [30].
• Prolactin replacement in bromocriptine-treated hamsters reversed the inhibitory effect of bromocriptine on hepatocyte lipogenesis and promoted dramatic lipogenic responses to insulin at 07.00 h [31].
• The S14 (spot 14) gene encodes a protein that is predominantly expressed in lipogenic tissues, such as the liver, white and brown adipose tissues and the lactating mammary glands [32].
• Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1 [33].

Other interactions of LPGP1

• Based on these findings, CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induce CRH negative feedback [34].
• Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue [4].
• Relatively little information exists on the ultimate molecular mechanisms by which the lipogenic enzyme Fatty Acid Synthase (FAS) is differentially overexpressed in a biologically aggressive subset of human malignancies [35].
• The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis [36].
• The "Spot 14" gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: implications for control of tumor metabolism [37].

Analytical, diagnostic and therapeutic context of LPGP1

• Immunohistochemistry showed that VSMC within atherosclerotic plaques express adipogenic and lipogenic markers, suggesting these pathways are present in vivo [38].
• White adipose tissue lipogenic activity was much more insulin responsive in the "insulinized" than in the control groups [39].
• Long-term studies in animal models have also shown that diets based on high-GI starches promote weight gain, visceral adiposity, and higher concentrations of lipogenic enzymes than do isoenergetic, macronutrientcontrolled, low-GI-starch diets [40].
• In the second part, we review some of the standard formulas of indirect calorimetry that offer the possibility to obtain more precise information such as the rate of oxidation of carbohydrates (CHO), lipids and proteins if some hypotheses are made on the intensity of lipogenic, ketogenic, and gluconeogenic processes [41].
• The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues [42].

References