A proinflammatory diet is associated with inflammatory gene expression among healthy, non-obese adults: Can social ties protect against the risks?

Highlights

• Diet was associated with inflammatory gene expression in middle-aged and older adults.

• Effects emerged only among those with less visceral fat and social participation.

• Diet had no effect on gene expression among more socially involved individuals.

Abstract

The Western diet, characterized by high intake of saturated fat, sugar, and salt, is associated with elevated inflammation and chronic disease risk. Few studies have investigated molecular mechanisms linking diet and inflammation; however, a small number of randomized controlled trials suggest that consuming an anti-inflammatory diet (i.e., a primarily plant-based diet rich in monounsaturated fat and lean protein) decreases proinflammatory gene expression. The current study investigated the association between everyday diet and proinflammatory gene expression, as well as the extent to which central adiposity and social involvement modulate risk. Participants were healthy middle-aged and older adults (N = 105) who completed a food frequency questionnaire and reported how many close social roles they have. Anthropometric measurements and blood samples also were collected; gene expression data were analyzed from LPS-stimulated peripheral blood mononuclear cells for interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. The inflammatory potential of each participant’s diet was calculated using the Dietary Inflammatory Index (DII®). Participants with higher DII® scores, indicating a more proinflammatory diet, had greater IL-6 (b = −0.02, SE = 0.008, p = .01), IL-1β (b = −0.01, SE = 0.006, p = .03), and TNF-α (b = −0.01, SE = 0.005, p = .04) gene expression if they had a smaller sagittal abdominal diameter (SAD); effects were not seen among those with higher SADs. Social involvement served a protective role, such that participants with smaller SADs had greater IL-6 (b = 0.01, SE = 0.004, p = .049) and IL-1β (b = 0.01, SE = 0.003, p = .045) gene expression only if they had less social involvement; there was no effect of diet on gene expression among those who reported greater social participation. Results are the first to demonstrate a link between self-reported diet and proinflammatory gene expression. Importantly, the effect of diet on gene expression depended upon both body fat composition and social participation, both of which have previously been linked directly with proinflammatory gene expression and inflammation.

Introduction

Mounting evidence suggests that a calorie-dense, nutrient-sparse diet is associated with chronic, systemic inflammation and poor health (Andersen and Fernandez, 2013, Panickar and Jewell, 2015). In rodent models, changing animals’ typical diet to one characterized by high saturated fat, salt, and sugar consumption (often referred to as a “Western diet”) reliably increases abdominal fat, insulin resistance, atherosclerosis, and inflammation (e.g., Christ et al., 2018, Nunemaker et al., 2008, Schreyer et al., 1998, Surwit et al., 1988). In humans, consuming a Western diet has been linked to chronic, low-grade inflammation and associated diseases such as cancer, heart disease, and diabetes (Huang et al., 2013, Thorburn et al., 2014). In contrast, a Mediterranean diet, which includes high fruit and vegetable consumption, moderate consumption of poultry, fish, eggs, and dairy, and low consumption of red meat and processed foods, appears to protect against chronic inflammation and related diseases (Casas et al., 2014).

Consistent evidence linking dietary factors and inflammation led to the development of the Dietary Inflammatory Index (DII®) to quantify the inflammatory potential of a person’s diet (Shivappa et al., 2014a). The DII® has now been associated with numerous health outcomes, including cardiovascular disease, cancer mortality, and all-cause mortality, even after controlling for factors such as physical activity level, BMI, and age (Hébert et al., 2019, Shivappa et al., 2017a, Shivappa et al., 2018b). For example, older women with higher DII® scores, indicating a more proinflammatory diet, had more severe atherosclerosis 36 months later and were at greater risk for heart disease-related death within a 15-year follow-up period compared to those who consumed a healthier diet (Bondonno et al., 2017). Evidence suggests that associations between the DII® and disease processes are driven by inflammation, as those with higher DII® scores also have higher serum inflammatory marker levels (Shivappa et al., 2017b, Shivappa et al., 2017c, Shivappa et al., 2015, Tabung et al., 2015).

Despite clear and consistent findings of a relationship between diet and inflammation, prior studies have not investigated underlying molecular mechanisms. Although scant, prior evidence suggests that certain dietary components may induce inflammation by altering inflammatory gene expression. For example, mice that were fed a high-fat diet for 12 weeks showed alterations in 30 genes known to influence inflammatory processes (Montalvany-Antonucci et al., 2018). A few small randomized controlled trials (RCTs) in humans provide convergent data. For example, in an RCT with 56 obese adults, those who were randomized to a Nordic diet, which bears many similarities to the Mediterranean diet, had lower proinflammatory gene expression in subcutaneous adipose tissue compared to those who ate a control diet; however, the groups showed no differences in baseline weight or weight loss (Kolehmainen et al., 2015). Similarly, an RCT with 20 overweight participants showed that those randomized to a diet high in saturated fat, typical of the Western diet, had greater increases in proinflammatory gene expression compared to those who ate a diet high in monounsaturated fat, common in the Mediterranean diet (van Dijk et al., 2009). However, prior studies have not investigated the link between people’s usual diets and inflammatory gene expression.

The negative effects of a poor diet may be modulated by abdominal obesity, which itself is a proinflammatory state linked with proinflammatory gene expression (Lopomo et al., 2016). Abdominal fat cells secrete proteins known to increase levels of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α (Trayhurn and Wood, 2004). Additionally, obese individuals show alterations in activation of transcription factors involved in inflammatory gene expression (Motawi et al., 2017, Rial et al., 2012). However, studies examining whether body composition augments the effect of diet on inflammation have provided mixed evidence. For example, a study of over 2,500 postmenopausal women found that those who consumed a more proinflammatory diet had higher plasma C-reactive protein (CRP) and TNF- α, and the effect was significantly stronger among obese participants (Tabung et al., 2015). On the other hand, data from a large, representative, national sample showed that a proinflammatory diet was more strongly associated with inflammation among non-obese individuals compared to those who were obese (Wirth et al., 2018). Thus, the interplay between diet and body fat remains unclear, warranting further exploration to identify potential factors that may increase diet-related risk. Importantly, many studies reporting an association between a proinflammatory diet and inflammatory markers control for BMI or weight (e.g., Phillips et al., 2018, Shivappa et al., 2015, Shivappa et al., 2017c) suggesting that obesity modulates, rather than drives, the association.

Further, lack of social integration has been reliably linked to inflammation and mortality (see Holt-Lunstad et al., 2015, Uchino et al., 2018 for meta-analyses). For example, in a landmark study, Cohen and colleagues (Cohen et al., 1997) demonstrated that individuals who had greater social role diversity (i.e., more types of social ties) were less likely to develop cold symptoms after being exposed to rhinoviruses, providing a clear example of social involvement’s positive impact on immune function. Research suggests that a person’s social environment may modulate inflammation via “social signal transduction,” whereby social factors regulate human gene expression via central nervous system activation (CNS) (Cole, 2014). Providing empirical support for the notion that social factors are linked to gene expression, one study found over 200 genes were differentially expressed in lonelier individuals compared to less lonely individuals, including up-regulation of genes known to promote inflammation (Cole et al., 2007). However, prior studies have not investigated the potential link between social involvement and inflammatory gene expression.

The current study investigated the associations among diet, inflammatory gene expression, and central adiposity. Previous work suggests that central adiposity may modulate the effect of diet on inflammation (Wirth et al., 2018); however it remains unclear whether the effect of diet is stronger among those with more visceral fat or those with less. Therefore, the interaction between sagittal abdominal diameter and diet in predicting proinflammatory gene expression was explored with no a priori hypotheses regarding directionality. Given its consistent association with inflammation, social participation also was included as a novel psychosocial moderator to determine whether it may serve a protective function. We hypothesized that a proinflammatory diet would be most strongly associated with heightened inflammatory gene expression among individuals who were at high risk based on their body composition and low social involvement. Therefore, a three-way interaction between diet, social participation, and central adiposity also was explored.