(P15-025-24) Relationships Between Gut Permeability, Adipose Tissue, Diet Quality, and Gut Microbiota With Inflammation in Normal-Weight and Metabolically Healthy Obesity

Objectives: Inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular risk. Yet, potential drivers of this inflammation remain unclear. We measured several parameters previously linked to low-grade inflammation (i.e., gut permeability, adipose tissue, diet quality, microbiota) in NWO and MHO, as well as healthy controls (CON) and at-risk individuals with metabolically unhealthy obesity (MUO).

Methods: Adults (N=80; n=20/group; 18-50 years) were grouped as CON (body mass index [BMI]18.5-24.9 kg/m², low body fat %, metabolically healthy); NWO (BMI 18.5-24.9 kg/m², high body fat %, no metabolic criteria); MHO (BMI ≥ 30 kg/m², high body fat %, metabolically healthy), or MUO (BMI ≥ 30 kg/m², high body fat %, metabolically unhealthy). Body fat % cutoffs were over/under 25% (M) or 35% (F). Metabolically healthy versus unhealthy was defined as 0-1 or 2+ metabolic syndrome criteria. Serum lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP) were used as indicators of gut permeability and inflammation, respectively. Total, visceral, and % body fat were measured with DXA. Healthy eating index (HEI) was calculated from a 3-day food record. Fecal microbiota composition was assessed via 16S sequencing on n=9-10/group. Data were analyzed with one-way ANOVA and Pearson correlations.

Results: For CRP, MUO > NWO > CON, and MHO was similar to MUO and NWO (p < 0.0001). LBP was similarly higher in MHO and MUO versus CON and NWO (p < 0.0001). HEI was higher in CON compared to MHO and MUO (p < 0.01). MUO had lower gut microbial diversity versus CON as measured by the Shannon Index (p < 0.05). In the full sample, LBP (r = 0.78; p < 0.0001), total fat mass (r = 0.49; p < 0.0001), visceral fat (r = 0.37; p < 0.01), and Shannon Index (r = -0.37; p < 0.05), but not HEI (r = -0.17; p = 0.14), were associated with CRP. Within study groups, LBP remained correlated with CRP in CON (r = 0.49; p < 0.05), MHO (r = 0.74; p < 0.01), and MUO (r = 0.88; p < 0.0001). In CON, HEI was inversely related to CRP (r = -0.53; p < 0.05). All other correlations became non-significant.

Conclusions: The marker of gut permeability LBP was linked to evidence of inflammation in MHO. Despite some evidence of inflammation, we did not observe relationships between health factors examined and CRP in NWO.

Funding Sources: American Heart Association