Mitochondrial bioenergetic pathways in blood leukocyte transcriptome decrease after intensive weight loss but are rescued following weight regain in female physique athletes.

Prolonged periods of energy deficit leading to weight loss induce metabolic adaptations resulting in reduced energy expenditure, but the mechanisms for energy conservation are incompletely understood. We examined 42 healthy athletic females (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m2 ) who volunteered into either a group dieting for physique competition (n = 25) or a control group (n = 17). The diet group substantially reduced their energy intake and moderately increased exercise levels to induce loss of fat mass that was regained during a voluntary weight regain period. The control group maintained their typical lifestyle habits and body mass as instructed. From the diet group, fasting blood samples were drawn at baseline (PRE), after 4- to 5-month weight loss (PRE-MID), and after 4- to 5-month weight regain (MID-POST) as well as from the control group at similar intervals. Blood was analyzed to determine leukocyte transcriptome by RNA-Sequencing and serum metabolome by nuclear magnetic resonance (NMR) platform. The intensive weight loss period induced several metabolic adaptations, including a prominent suppression of transcriptomic signature for mitochondrial OXPHOS and ribosome biogenesis. The upstream regulator analysis suggested that this reprogramming of cellular energy metabolism may be mediated via AMPK/PGC1-α signaling and mTOR/eIF2 signaling-dependent pathways. Our findings show for the first time that prolonged energy deprivation induced modulation of mitochondrial metabolism can be observed through minimally invasive measures of leukocyte transcriptome and serum metabolome at systemic level, suggesting that adaptation to energy deficit is broader in humans than previously thought.

Substantial Fat Loss in Physique Competitors Is Characterized by Increased Levels of Bile Acids, Very-Long Chain Fatty Acids, and Oxylipins.

Weight loss and increased physical activity may promote beneficial modulation of the metabolome, but limited evidence exists about how very low-level weight loss affects the metabolome in previously non-obese active individuals. Following a weight loss period (21.1 ± 3.1 weeks) leading to substantial fat mass loss of 52% (−7.9 ± 1.5 kg) and low body fat (12.7 ± 4.1%), the liquid chromatography-mass spectrometry-based metabolic signature of 24 previously young, healthy, and normal weight female physique athletes was investigated. We observed uniform increases (FDR < 0.05) in bile acids, very-long-chain free fatty acids (FFA), and oxylipins, together with reductions in unsaturated FFAs after weight loss. These widespread changes, especially in the bile acid profile, were most strongly explained (FDR < 0.05) by changes in android (visceral) fat mass. The reported changes did not persist, as all of them were reversed after the subsequent voluntary weight regain period (18.4 ± 2.9 weeks) and were unchanged in non-dieting controls (n = 16). Overall, we suggest that the reported changes in FFA, bile acid, and oxylipin profiles reflect metabolic adaptation to very low levels of fat mass after prolonged periods of intense exercise and low-energy availability. However, the effects of the aforementioned metabolome subclass alteration on metabolic homeostasis remain controversial, and more studies are warranted to unravel the complex physiology and potentially associated health implications. In the end, our study reinforced the view that transient weight loss seems to have little to no long-lasting molecular and physiological effects.

Resistance Training Induces Antiatherogenic Effects on Metabolomic Pathways.

INTRODUCTION: Arising evidence suggests that resistance training has the potential to induce beneficial modulation of biomarker profile. To date, however, only immediate responses to resistance training have been investigated using high-throughput metabolomics whereas the effects of chronic resistance training on biomarker profile have not been studied in detail. METHODS: A total of 86 recreationally active healthy men without previous systematic resistance training background were allocated into (i) a resistance training (RT) group (n = 68; age, 33 ± 7 yr; body mass index, 28 ± 3 kg·m) and (ii) a non-RT group (n = 18; age, 31 ± 4 yr; body mass index, 27 ± 3 kg·m). Blood samples were collected at baseline (PRE), after 4 wk (POST-4wk), and after 16 wk of resistance training intervention (POST-16wk), as well as baseline and after the non-RT period (20-24 wk). Nuclear magnetic resonance-metabolome platform was used to determine metabolomic responses to chronic resistance training. RESULTS: Overall, the resistance training intervention resulted in favorable alterations (P < 0.05) in body composition with increased levels of lean mass (~2.8%), decreased levels of android (~9.6%), and total fat mass (~7.5%). These changes in body composition were accompanied by antiatherogenic alterations in serum metabolome profile (false discovery rate < 0.05) as reductions in non-high-density lipoprotein cholesterol (e.g., free cholesterol, remnant cholesterol, intermediate-density lipoprotein cholesterols, low-density lipoprotein cholesterols) and related apolipoprotein B, and increments in conjugated linoleic fatty acids levels were observed. Individuals with the poorest baseline status (i.e., body composition, metabolome profile) benefitted the most from the resistance training intervention. CONCLUSIONS: In conclusion, resistance training improves cardiometabolic risk factors and serum metabolome even in previously healthy young men. Thus, suggesting attenuated risk for future cardiovascular disease.

Food neophobia associates with poorer dietary quality, metabolic risk factors, and increased disease outcome risk in population-based cohorts in a metabolomics study.

BACKGROUND: Food neophobia is considered a behavioral trait closely linked to adverse eating patterns and reduced dietary quality, which have been associated with increased risk of obesity and noncommunicable diseases. OBJECTIVES: In a cross-sectional and prospective study, we examined how food neophobia is associated with dietary quality, health-related biomarkers, and disease outcome incidence in Finnish and Estonian adult populations. METHODS: The study was conducted based on subsamples of the Finnish DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) cohort (n = 2982; age range: 25-74 y) and the Estonian Biobank cohort (n = 1109; age range: 18-83 y). The level of food neophobia was assessed using the Food Neophobia Scale, dietary quality was evaluated using the Baltic Sea Diet Score (BSDS), and biomarker profiles were determined using an NMR metabolomics platform. Disease outcome information was gathered from national health registries. Follow-up data on the NMR-based metabolomic profiles and disease outcomes were available in both populations. RESULTS: Food neophobia associated significantly (adjusted P < 0.05) with health-related biomarkers [e.g., ω-3 (n-3) fatty acids, citrate, α1-acid glycoprotein, HDL, and MUFA] in the Finnish DILGOM cohort. The significant negative association between the severity of food neophobia and ω-3 fatty acids was replicated in all cross-sectional analyses in the Finnish DILGOM and Estonian Biobank cohorts. Furthermore, food neophobia was associated with reduced dietary quality (BSDS: ß: -0.03 ± 0.006; P = 8.04 × 10-5), increased fasting serum insulin (ß: 0.004 ± 0.0013; P = 5.83 × 10-3), and increased risk of type 2 diabetes during the ∼8-y follow-up (HR: 1.018 ± 0.007; P = 0.01) in the DILGOM cohort. CONCLUSIONS: In the Finnish and Estonian adult populations, food neophobia was associated with adverse alteration of health-related biomarkers and risk factors that have been associated with an increased risk of noncommunicable diseases. We also found that food neophobia associations with ω-3 fatty acids and associated metabolites are mediated through dietary quality independent of body weight.

Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss.

Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m2) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 ± 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 ± 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated.