Dietary fat has several essential functions in the human body. First, it functions as a supply of energy and structural components for the cells and second, it functions as a regulator of gene expression, which influences lipid, carbohydrate, and protein metabolism, along with cell growth and differentiation. The effects of fatty acids on gene expression are cell-specific and influenced by structure and metabolism. Fatty acids interact with the genome. They regulate PPAR, and the activity or nuclear abundance like SREBP. Fatty acids bind directly with one another to regulate gene expression.

What’s the role of fatty acids towards disease pathogenesis?

Alternately, fatty acids behave on gene expression through their effects on specific enzyme-mediated pathways, such as cyclooxygenase, lipoxygenase, protein kinase C, or sphingomyelinase signal transduction pathways, or through pathways that require changes in tissue lipid to lipid raft composition which affect G-protein receptor or tyrosine kinase-linked receptor signaling. Additional definition of these fatty acid-regulated pathways can offer insight into the role dietary fat plays in human health as well as the beginning and growth of many chronic diseases, such as coronary artery disease and atherosclerosis, dyslipidemia and inflammation, obesity and diabetes, cancer, major depressive disorders, and schizophrenia. The effects of fatty acids on gene expression, however, have been widely described on inflammatory bowel disease, or IBD.

Fatty Acids and Gene Expression

The effect of fatty acids on gene expression was previously determined to result mainly from changes in tissue phospholipids or eicosanoid production. More recently, the discovery of nuclear receptors; such as peroxisome proliferator-activated receptors, or PPARs, and their regulation by fatty acids, has significantly altered this view. PPARs are ligand activated transcription factors that upon heterodimerization with the retinoic X receptor, or RXR, comprehend PPAR response elements in the promoter regions of different genes, that have an impact on gene transcription. PPARs bind various ligands, including nonsteroidal anti inflammatory medications, or NSAIDS, thiazolidinediones (antidiabetic agents) along with PUFAs and their metabolites. Several subtypes of the receptor are recognized (?,?,?) and are expressed in several different cells. PPAR? is extracted from the adrenal gland, with most of its numbers observed in the colon.

PPAR? has been implicated in the regulation of inflammation, and it has become a potential therapeutic goal in treating inflammatory diseases, such as IBD. It has been suggested that people with ulcerative colitis, or UC, have a mucosal deficit in PPAR? that could bring about the development of their own disease. Analysis of the mRNA and proteins within colonic biopsies demonstrated decreased levels of PPAR? in UC patients in comparison with Crohn’s patients or healthy subjects.

Using colon cancer lines, it has been demonstrated that PPAR ligands attenuate cytokine gene expression by inhibiting NF-?B via an I?B determined mechanism. Further research studies imply that PPAR activators inhibit COX2 by interruption with NF-?B. PPARs impair interactions with STAT and other signaling pathways as well as the AP-1 signaling pathway.

Animal studies support using PPAR for autoimmune inflammation. Inflammation decreased by ligands for PPAR. The direction of PPAR and RXR agonists synergistically reduced TNBS-induced colitis, together with improved macroscopic and histologic scores, reductions in TNF? and IL-1? mRNA, and diminished NF-?B DNA binding actions. Though clinical evidence is limited, the results of an open source research study with rosiglitazone, a PPAR? ligand as therapy for UC, demonstrated that 27 percent of patients achieved remission after 12 weeks of therapy. Thus, PPAR? ligands may represent a cure for UC, where double-blind, placebo-controlled, randomized trials have been warranted.

Of substantial curiosity, the capability to regulate PPAR nutritionally has been examined. Dietary PUFA demonstrated an impact during the regulation of transcription factors on gene expression. Fatty acid regulation of PPAR was originally detected by Gottlicher et al.. A choice of fatty acids, like eicosanoids, and metabolites are proven to activate PPAR. Both PPAR? and PPAR? bind mono- and polyunsaturated fatty acids. Thus, the anti inflammatory effects of n3 PUFA may entail PPAR and its interruption with NF?B, rather than only changes in eicosanoid synthesis.

Conclusion

Fatty acids regulate gene expression involved in lipid and energy metabolism. Polyunsaturated fatty acids, or PUFA, though not saturated or polyunsaturated FA, suppress the induction of lipogenic genes by inhibiting their expression and processing of SREBP-1c. This impact of PUFA suggests that SREBP-1c may regulate the synthesis of fatty acids to glycerolipids, among others. PPARalpha has a role in the adaptation to fasting by inducing ketogenesis in mitochondria. During fasting, fatty acids are considered as ligands of PPARalpha. Dietary PUFA, except for 18:2 n-6, are extremely prone to induce fatty acid oxidation enzymes through PPARalpha because of specific mechanisms. Signaling functions of PPARalpha pPARalpha is needed for controlling the synthesis of fatty acids. Further research is needed to conclude the full effects of fatty acids in relation to the regulation of transcription factors for gene expression in inflammatory bowel disease, or IBD.

Information referenced from the National Center for Biotechnology Information (NCBI) and the National University of Health Sciences. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

By Dr. Alex Jimenez

Additional Topics: Wellness

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress

Inflammatory bowel disease, or IBD, is a term used to describe inflammation of the gastrointestinal mucosa of unknown etiology. There are a selection of hypotheses associated to the development and perpetuation of IBD. Three main theories emerge from the literature. The first implicates a persistent intestinal infection; the second demonstrates that the upcoming signs of IBD are due to a defective mucosal barrier to luminal antigens; and the next suggests a dysregulated host immune response to ubiquitous antigens.

What are the nutritional components, if any, behind inflammatory bowel disease?

It is believed that IBD has both genetic and environmental components, therefore it’s immunologically mediated. Information gathered from IBD patients showing cytokine profiles, permeability defects, response to treatment and natural history of disease, may indicate a heterogeneous group of disorders that fall under the headings of ulcerative colitis, or UC, and Crohn’s disease, or CD. Previous epidemiological data on diet in UC and CD are conflicting, partly as a result of the heterogeneity of those diseases, making it difficult to get reliable statistics and publication bias, such as in the case of negative structures from breastfeeding.

Glutamine, Fiber and Fatty Acids

Diets high in glutamine, a significant source of energy for enterocytes, in addition to being the preferred fuel of the small intestine, are used with varying success. Glutamine is bekieved to exert its trophic effects on the small intestine by increasing protein synthesis and producing alanine for enteric gluconeogenesis. There is proof that glutamine protects the small intestinal mucosa during acute disease. However, oral glutamine supplements do not restore to normal the increased intestinal permeability discovered in patients with CD and these supplements do not beneficially affect the sufferers’ CDAI or C-reactive protein, also abbreviated as CRP, levels. Similarly, a randomized controlled trial demonstrated no benefit was connected to the usage of glutamine-enriched polymeric formulas in children with CD.

In animal research studies, dietary fiber has been implicated in keeping the integrity of the intestine, as well as in preventing bacterial translocation from the gut to the mesenteric lymph nodes. Short-chain fatty acids (SCFA, C1 to C6 natural fatty acids), are created by the fermentation of dietary polysaccharides in the common anaerobic bacteria in the colon. These SCFA are a source of energy for the colonocytes, which together improve sodium and water absorption, and promote blood circulation. Decreased quantities of SCFA, particularly butyrate, and a defect in the oxidation of butyrate from colonocytes, are indicated as a mechanism in the pathogenesis of inflammatory bowel disease. Evidence to support that concept requires the observation of the oxidation of C-labelled butyrate, demonstrated to decrease in patients with active UC in comparison with healthy controls. However, researchers have failed to reveal the differences between UC patients and controls in the oxidation of rectally administered C-labelled butyrate.

TPN supplemented with SCFA improved function adaptation to intestinal resection in rats. It remains to be discovered when patients with short bowel syndrome may make the most of SCFA.

Butyrate (C4 fatty acid) administered to UC patients contributed to remission levels like corticosteroids and mesalamine. In patients with CD, both intestinal biopsies and lamina propria cells packaged with butyrate had substantially decreased levels of inflammatory cytokines (TNF), possibly due to a reduction in NF?B stimulation and I?B degradation.

Eicosanoids are inflammatory mediators, which have also been implicated in the pathogenesis of chronic inflammatory damage in the intestine. Specimens from patients with IBD show enhanced eicosanoid formation. High dietary intake of omega-6 polyunsaturated fatty acids, abbreviated as PUFAs, which reduces omega-3 intake, and may contribute to IBD development. The benefits of fish oil, which contain n3 fatty acids, that were shown in certain inflammatory disorders, such as psoriasis and rheumatoid arthritis. Epidemiological observations of this very low prevalence of IBD in Japanese and Inuit populations consuming substantial n3 fatty acid fish provided a justification for utilizing n3 fatty acids in IBD. The n3 fatty acids are considered to compete with n6 fatty acids as precursors of eicosanoid synthesis. The n3 products reveal a series of 5 leukotrienes, which have considerably less physiological activity when compared with the arachidonate established series 4 counterparts. In addition, fish oil might have an anti inflammatory effect.

Rats fed with fish oil that had TNBS-induced inflammatory lesions in the intestine showed less prostaglandin- and leukotriene-mediated resistant response. Parenteral lipid emulsions enhanced with n3 fatty acids reduce diarrhea, weaken morphological changes and decreased colonic concentrations of inflammatory mediators in an animal model of acetic acid induced colitis.

Loeschke et al conducted a placebo-controlled trial of n3 fatty acids in preventing relapse in UC. Patients in remission who got n3 fatty acids experienced fewer relapses than did those receiving placebo. Unfortunately, the favorable results of this research study did not last throughout the total amount of the two year research, possibly due to diminished compliance punctually. In a multicenter placebo controlled relapse prevention trial, Belluzzi et al found a significant drop in the relapse rate in CD patients given an exceptional formula designed to allow postponed ileal release of n3 fatty acids. A fish oil diet has been shown to increase eicosapentanoic and docosahexanoic acids in the intestinal mucosal lipids of IBD sufferers, also demonstrating a reduction in arachadonic acid. A gain in the synthesis of leukotriene B5 along with a 53 percent decrease of leukotriene B4 was shown in UC patients, whereas the fish oil treatment revealed a nonsignificant trend to faster remission. Fish oil supplementation results in clinical improvement of active mild to moderate disease, but was not associated with a significant reduction in leukotriene B4 production. Consequently, fish oil supplementation of the diet may provide some short-term benefit to people with CD or UC. Using probiotics and prebiotics has received much attention; the interested reader is referred to recent reviews in this area.

Clinical Implications

It is widely known that nutritional deficiencies are common in people with CD and UC, and people have to be expected, diagnosed and treated. There are no special diets which may be recommended for all patients with IBD; dietary therapy needs to be individualized. TPN or TEN may be necessary to restore nutrient equilibrium in selected IBD patients with malnutrition, but in adults these interventions do not provide an essential decision to modify disease activity. The omega-3 PUFAs in fish oil may reduce disease activity in UC and CD when used at the short term together with regular medical therapy. Their mechanism of action is to enhance the activity of the amino acids PPAR, or peroxisome proliferator-activated receptors, in the intestine, inhibiting the AP-1 signaling pathway and NF-?B, weakening pro-inflammatory cytokine receptor expression. Future research will focus on the identification and use of certain dietary lipids to reduce intestinal inflammatory activity and also to maintain long-term disease remission.

Information referenced from the National Center for Biotechnology Information (NCBI) and the National University of Health Sciences. The scope of our information is limited to chiropractic and spinal injuries and conditions. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

By Dr. Alex Jimenez

Additional Topics: Wellness

Overall health and wellness are essential towards maintaining the proper mental and physical balance in the body. From eating a balanced nutrition as well as exercising and participating in physical activities, to sleeping a healthy amount of time on a regular basis, following the best health and wellness tips can ultimately help maintain overall well-being. Eating plenty of fruits and vegetables can go a long way towards helping people become healthy.

WELLNESS TOPIC: EXTRA EXTRA: Managing Workplace Stress