Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice.
Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclusive. Our objective was to determine whether Lcn2 deficiency-induced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.
['Singh|Vishal|V|', 'Galla|Sarah|S|', 'Golonka|Rachel M|RM|', 'Patterson|Andrew D|AD|', 'Chassaing|Benoit|B|0000-0002-4285-769X', 'Joe|Bina|B|', 'Vijay-Kumar|Matam|M|0000-0002-8732-0167']
D000273:Adipose Tissue D050154:Adiposity D000375:Aging D000818:Animals D001786:Blood Glucose D059305:Diet, High-Fat D004195:Disease Models, Animal D064806:Dysbiosis D050171:Dyslipidemias D005260:Female D000069196:Gastrointestinal Microbiome D006706:Homeostasis D000071068:Lipocalin-2 D008297:Male D024821:Metabolic Syndrome D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009765:Obesity
insulin resistance dyslipidemias microbial-host interactions obesity