Impact in Plasma Metabolome as Effect of Lifestyle Intervention for Weight-Loss Reveals Metabolic Benefits in Metabolically Healthy Obese Women

Abstract

Little is known regarding metabolic benefits of weight loss (WL) on the metabolically healthy obese (MHO) patients. We aimed to examine the impact of a lifestyle weight loss (LWL) treatment on the plasma metabolomic profile in MHO individuals. Plasma samples from 57 MHO women allocated to an intensive LWL treatment group (TG, hypocaloric Mediterranean diet and regular physical activity, n = 30) or to a control group (CG, general recommendations of a healthy diet and physical activity, n = 27) were analyzed using an untargeted H NMR metabolomics approach at baseline, after 3 months (intervention), and 12 months (follow-up). The impact of the LWL intervention on plasma metabolome was statistically significant at 3 months but not at follow-up and included higher levels of formate and phosphocreatine and lower levels of LDL/VLDL (signals) and trimethylamine in the TG. These metabolites were also correlated with WL. Higher myo-inositol, methylguanidine, and 3-hydroxybutyrate, and lower proline, were also found in the TG; higher levels of hippurate and asparagine, and lower levels of 2-hydroxybutyrate and creatine, were associated with WL. The current findings suggest that an intensive LWL treatment, and the consequent WL, leads to an improved plasma metabolic profile in MHO women through its impact on energy, amino acid, lipoprotein, and microbial metabolism.

Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies

“…The second block includes five studies focused on studying the differential responses of obese and non-obese subjects to dietary challenges (Table 2 ) (Badoud et al 2015b ; Baker et al 2015 ; Geidenstam et al 2014 ; Bak et al 2018 ). The third block comprises three studies that used metabolomics to predict weight loss (Geidenstam et al 2017a , b ; Stroeve et al 2016 ) and 11 randomized clinical trials (RCTs) aimed to assess the effects of weight loss interventions (both hypocaloric diet programs and exercise interventions) on the metabolomic profiles of overweight or obese human subjects (Table 2 ) (Almanza-Aguilera et al 2018 ; Duft et al 2017 ; Kang et al 2018 ; Leal-Witt et al 2018 ; Meucci et al 2017 ; Mills et al 2019 ; Munukka et al 2018 ; Palau-Rodriguez et al 2019 ; Perez-Cornago et al 2014 ; Zheng et al 2016a , b ). Additionally, the fourth block includes 11 articles that studied the effects of specific dietary patterns or dietary compounds on obesity-related metabolic alterations in humans, such as inflammation or oxidative stress (Table 3 ) (Baldrick et al 2018 ; Gu et al 2013 ; Hernández-Alonso et al 2019 ; Hibberd et al 2019 ; Kim et al 2013 ; Kim et al 2017 ; Mayengbam et al 2019 ; Nieman et al 2012a , b ; Romo-Hualde et al 2018 ; Xu et al 2018 ).…”

“…Eight articles (Leal-Witt et al 2018 ; Kang et al 2018 ; Palau-Rodriguez et al 2019 ; Mills et al 2019 ; Almanza-Aguilera et al 2018 ; Perez-Cornago et al 2014 ; Zheng et al 2016a , b ) focused on determining the effect of weight loss on the metabolomics profiles of overweight and obese individuals. The article from Zheng et al ( 2016b ) was approached as two studies because the study design including two different cohorts, see below).…”

“…Other short-term intervention showed significantly higher increases in plasma of MCAC and long-chain AC (LCAC) and lysoPC (20:4) in overweight adults with a low-calorie diet than their control group (Table 2 ) (Kang et al 2018 ). A study including MHO women undergoing a lifestyle weight loss treatment for 3 months (and a 12-month follow-up) showed an altered plasma metabolome (Almanza-Aguilera et al 2018 ). Namely, higher levels of formate and phosphocreatine and lower levels of trimethylamine were observed in the treatment group than in the control group.…”

“…TMAO has been reported as biomarker of obesity (Zheng et al 2016a , b ), CVD risk (Bennett et al 2013 ; Trøseid et al 2015 ) and it is originated from microbial activity (Leal-Witt et al 2018 ; Zheng et al 2016a , b ). Its precursor trimethylamine (TMA) provided from the microbial metabolism of dietary carnitine and choline, decreased in weight loss conditions (Almanza-Aguilera et al 2018 ). TMA is oxidized by hepatic flavin-containing monooxygenases to form TMAO, which has been shown to be both proatherogenic and associated with CVD (Tang et al 2013 ; Wang et al 2011 ).…”

“…TMA is oxidized by hepatic flavin-containing monooxygenases to form TMAO, which has been shown to be both proatherogenic and associated with CVD (Tang et al 2013 ; Wang et al 2011 ). Almanza-Aguilera et al ( 2018 ) reported that lower levels of TMA after weight loss associated to lifestyle intervention are related to either a lower intake of its dietary precursors (i.e., eggs and meat) (Koeth et al 2013 ; Tang et al 2013 ) or modulation of choline and carnitine metabolism. Similarly, TMAO was reduced in urine after a lifestyle intervention program in obese prepubertal children (Leal-Witt et al 2018 ).…”