Sarah Misyak

Conjugated Linoleic Acid Ameliorates Inflammation-Induced Colorectal Cancer in Mice through Activation of PPARγ

Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.

Immune-Mediated Mechanisms Potentially Regulate the Disease Time-Course of Duchenne Muscular Dystrophy and Provide Targets for Therapeutic Intervention

Duchenne muscular dystrophy is a lethal muscle‐wasting disease that affects boys. Mutations in the dystrophin gene result in the absence of the dystrophin glycoprotein complex (DGC) from muscle plasma membranes. In healthy muscle fibers, the DGC forms a link between the extracellular matrix and the cytoskeleton to protect against contraction‐induced membrane lesions and to regulate cell signaling. The absence of the DGC results in aberrant regulation of inflammatory signaling cascades. Inflammation is a key pathological characteristic of dystrophic muscle lesion formation. However, the role and regulation of this process in the disease time‐course has not been sufficiently examined. The transcription factor nuclear factor‐κB has been shown to contribute to the disease process and is likely involved with increased inflammatory gene expression, including cytokines and chemokines, found in dystrophic muscle. These aberrant signaling processes may regulate the early time‐course of inflammatory events that contribute to the onset of disease. This review critically evaluates the possibility that dystrophic muscle lesions in both patients with Duchenne muscular dystrophy and mdx mice are the result of immune‐mediated mechanisms that are regulated by inflammatory signaling and also highlights new therapeutic directions.

Dysregulated Intracellular Signaling and Inflammatory Gene Expression During Initial Disease Onset in Duchenne Muscular Dystrophy

Evans NP, Misyak SA, Robertson JL, Bassaganya-Riera J, Grange RW: Dysregulated intracellular signaling and inflammatory gene expression during initial disease onset in Duchenne muscular dystrophy. Duchenne muscular dystrophy is a debilitating genetic disorder characterized by severe muscle wasting and early death in affected boys. The primary cause of this disease is mutations in the dystrophin gene that result in the absence of the protein dystrophin and the associated dystrophin-glycoprotein complex in the plasma membrane of muscle fibers. In normal muscle, this complex forms a link between the extracellular matrix and the cytoskeleton that is thought to protect muscle fibers from contraction-induced membrane lesions and to regulate cell signaling cascades. Although the primary defect is known, the mechanisms that initiate disease onset have not been characterized. Data collected during early maturation suggest that inflammatory and immune responses are key contributors to disease pathogenesis and may be initiated by aberrant signaling in dystrophic muscle. However, detailed time course studies of the inflammatory and immune processes are incomplete and need to be characterized further to understand the disease progression. The purposes of this review are to examine the possibility that initial disease onset in dystrophin-deficient muscle results from aberrant inflammatory signaling pathways and to highlight the potential clinical relevance of targeting these pathways to treat Duchenne muscular dystrophy.

Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

Mounting evidence suggests that the risk of developing colorectal cancer (CRC) is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohns Disease (CD) or Ulcerative Colitis (UC) have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

Progress Evaluation for the Restaurant Industry Assessed by a Voluntary Marketing-Mix and Choice-Architecture Framework That Offers Strategies to Nudge American Customers toward Healthy Food Environments, 2006–2017

Consumption of restaurant food and beverage products high in fat, sugar and sodium contribute to obesity and non-communicable diseases. We evaluated restaurant-sector progress to promote healthy food environments for Americans. We conducted a desk review of seven electronic databases (January 2006–January 2017) to examine restaurant strategies used to promote healthful options in the United States (U.S.). Evidence selection (n = 84) was guided by the LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and verified by data and investigator triangulation. A marketing-mix and choice-architecture framework was used to examine eight voluntary strategies (i.e., place, profile, portion, pricing, promotion, healthy default picks, priming or prompting and proximity) to evaluate progress (i.e., no, limited, some or extensive) toward 12 performance metrics based on available published evidence. The U.S. restaurant sector has made limited progress to use pricing, profile (reformulation), healthy default picks (choices), promotion (responsible marketing) and priming and prompting (information and labeling); and some progress to reduce portions. No evidence was available to assess progress for place (ambience) and proximity (positioning) to promote healthy choices during the 10-year review period. Chain and non-chain restaurants can apply comprehensive marketing-mix and nudge strategies to promote healthy food environments for customers.

A Comparison of Fruits, Vegetables, Sugar-Sweetened Beverages, and Desserts in the Packed Lunches of Elementary School Children

BACKGROUND An estimated 40% of children bring a packed lunch to school. These lunches are not required to meet nutrition standards. The aim of this study was to compare differences in the nutritional quality of elementary packed lunches by the presence or absence of sugar-sweetened beverages (SSB), desserts, and fruits and vegetables (FVs). METHODS Observational data for prekindergarten and kindergarten packed lunches were collected from three schools in rural Virginia for 5 consecutive school days and analyzed for macro- and micronutrients and by the presence or absence of food and beverage items. RESULTS Of the 561 packed lunch observations collected, 41.7% contained no FV, 41.2% contained an SSB, and 61.1% contained a dessert. The nutrient profile of packed lunches with at least one fruit or vegetable had significantly higher levels of carbohydrate, fiber, sugar, vitamin A, and vitamin C. Packed lunches containing an SSB had significantly higher levels of sugar and vitamin C and significantly lower levels of protein, fiber, vitamin A, calcium, and iron. Packed lunches containing a dessert had significantly higher levels of energy, carbohydrate, fat, saturated fat, sodium, sugar, vitamin C, and iron and significantly lower levels of vitamin A. CONCLUSIONS Additional research is needed to fully understand parent and child motivations for packing lunches and the decision processes that influence the inclusion of food items. The development of packed lunch interventions, encouragement of National School Lunch Program participation, or enactment of school policies to increase the nutritional value of packed lunches is warranted.

Dietary Intake Changes in Response to a Sugar-Sweetened Beverage Reduction Trial for Various Supplemental Nutrition Assistance Program (SNAP) Eligibility Groups

Objective: To examine dietary intake differences resulting from a sugar‐sweetened beverage reduction intervention by 3 Supplemental Nutrition Assistance Program (SNAP) participation groups: SNAP participants (n = 56), income‐eligible nonparticipants (n = 30), and income‐ineligible nonparticipants (n = 60). Methods: Adults in southwest Virginia were enrolled in a 6‐month behavioral trial. The researchers collected SNAP enrollment status and 3 24‐hour dietary recalls at baseline and 6 months. Repeated‐measures ANOVAs were used to assess differences in dietary intake among SNAP participation groups. Results: No significant group × time differences were found for energy density, Healthy Eating Index scores, Healthy Beverage Index scores, or intake of total calories, added sugars, and sugar‐sweetened beverages. However, several within‐group improvements were noted: income‐ineligible nonparticipants and SNAP participants improved in more areas compared with income‐eligible nonparticipants, including intake of total calories, added sugars, and sugar‐sweetened beverages. Conclusions and Implications: This exploratory analysis suggests that the overall effectiveness of a sugar‐sweetened beverage intake reduction intervention was not influenced by SNAP eligibility and participation status, because there were no significant group by time differences over the intervention. It is important to recognize for future programs that different approaches to improving dietary intake may be needed to match the characteristics of this audience better. This may be accomplished by attempting to decrease the disparity gap between income‐eligible nonparticipants and those receiving SNAP or who are income ineligible through the use of programs such as SIPsmartER.

Reliability of a Market Basket Assessment Tool (MBAT) for Use in SNAP-Ed Healthy Retail Initiatives

Objective: To evaluate the reliability of the Market Basket Assessment Tool (MBAT) for assessing the availability of fruits and vegetables, low‐fat or nonfat dairy and eggs, lean meats, whole‐grain products, and seeds, beans, and nuts in Supplemental Nutrition Assistance Program–authorized retail environments. Methods: Different trained raters used the MBAT simultaneously at 14 retail environments to measure interrater reliability. Raters returned to 12 retail environments (85.7%) 1 week later to measure test‐retest reliability. Data were analyzed using paired‐sample t tests and correlations. Results: No significant differences were found for interrater reliability or test‐retest reliability for individual categories (mean differences, 0.0 to 0.3 ± 0.2 points) or total score (mean difference, 0.5 ± 0.4 points and (mean differences, 0.0 to 0.3 ± 0.3 points) or total score (mean difference, 0.8 ± 0.4 points), respectively. Conclusions and Implications: Future steps include validation of the MBAT. A low‐burden tool can facilitate evaluation of efforts to promote healthful foods in retail environments.