RESUMEN
Background: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a group of fatty acids with potential anti-inflammatory and anti-diabetic effects. The blood levels of FAHFAs and their regulation in humans have hardly been studied. Objective: We aimed to investigate serum FAHFA levels in well-characterized human cohorts, to evaluate associations with age, sex, BMI, weight loss, diabetic status, and diet. Methods: We analyzed levels of stearic-acid-9-hydroxy-stearic-acid (9-SAHSA), oleic-acid-9-hydroxy-stearic-acid (9-OAHSA) and palmitic-acid-9-hydroxy-palmitic-acid (9-PAHPA) as well as different palmitic acid-hydroxy-stearic-acids (PAHSAs) by HPLC-MS/MS with the use of an internal standard in various cohorts: A cohort of different age groups (18-25y; 40-65y; 75-85y; Σ n = 60); severely obese patients undergoing bariatric surgery and non-obese controls (Σ n = 36); obese patients with and without diabetes (Σ n = 20); vegetarians/vegans (n = 10) and omnivores (n = 9); and young men before and after acute overfeeding with saturated fatty acids (SFA) (n = 15). Results: Omnivores had substantially higher FAHFA levels than vegetarians/vegans [median (25th percentile; 75th percentile) tFAHFAs = 12.82 (7.57; 14.86) vs. 5.86 (5.10; 6.71) nmol/L; P < 0.05]. Dietary overfeeding by supplementation of SFAs caused a significant increase within 1 week [median tFAHFAs = 4.31 (3.31; 5.27) vs. 6.96 (6.50; 7.76) nmol/L; P < 0.001]. Moreover, obese patients had lower FAHFA levels than non-obese controls [median tFAHFAs = 3.24 (2.80; 4.30) vs. 5.22 (4.18; 7.46) nmol/L; P < 0.01] and surgery-induced weight loss increased 9-OAHSA level while other FAHFAs were not affected. Furthermore, significant differences in some FAHFA levels were found between adolescents and adults or elderly, while no differences between sexes and between diabetic and non-diabetic individuals were detected. Conclusions: FAHFA serum levels are strongly affected by high SFA intake and reduced in severe obesity. Age also may influence FAHFA levels, whereas there was no detectable relation with sex and diabetic status. The physiological role of FAHFAs in humans remains to be better elucidated. Trial Registration: All studies referring to these analyses were registered in the German Clinical Trial Register (https://www.drks.de/drks_web/) with the numbers DRKS00009008, DRKS00010133, DRKS00006211, and DRKS00009797.
RESUMEN
BACKGROUND: Recent studies have suggested that obesity is associated with an increased intestinal permeability as well as an altered microbiota profile. These conditions can promote the translocation of lipopolysaccharide into the circulation and, subsequently, contribute to the observed systemic inflammation. Our aim was to assess gut permeability in patients with obesity compared to non-obese subjects as well as after excessive weight loss following laparoscopic sleeve gastrectomy (LSG). METHODS: We analyzed the dietary intake, metabolic and inflammatory markers, gut permeability (four-probe sugar test), and microbiota composition in 17 morbidly obese patients before and after LSG as well as in 17 age- and gender-matched non-obese subjects. Additionally, we compared gut permeability and inflammatory markers in patients of different stages of obesity. RESULTS: Patients with obesity showed elevated levels of C-reactive protein and lipopolysaccharide-binding protein as compared to non-obese subjects, but no differences were noted for gut permeability between these two groups. LSG led to improvements in metabolic and inflammatory parameters in the obese patients. Moreover, gastroduodenal as well as small intestinal permeability decreased, whereas colonic permeability increased after surgery. Regarding gut microbiota, differences were noted for main phyla and alpha-diversity between non-obese and obese subjects. After surgery, the composition of the microbiota showed a tendency toward the pattern of the non-obese group. CONCLUSIONS: Gut permeability is not dependent on body mass index, whereas weight loss after LSG initiates distinct changes in gastroduodenal, intestinal, and colonic permeability. These changes do not seem to be associated with changes in the microbiota composition. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: The trials were registered at https://www.drks.de/drks_web/ with the number DRKS00009008 and DRKS00006210.
Asunto(s)
Gastrectomía , Mucosa Intestinal/metabolismo , Obesidad Mórbida/cirugía , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Microbioma Gastrointestinal/fisiología , Humanos , Inflamación/sangre , Inflamación/complicaciones , Inflamación/microbiología , Inflamación/cirugía , Mediadores de Inflamación/sangre , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Intestinos/microbiología , Intestinos/patología , Intestinos/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Morbilidad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/metabolismo , Obesidad Mórbida/microbiología , Permeabilidad , Proyectos Piloto , Pérdida de Peso/fisiologíaRESUMEN
Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.