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.

Weight loss induces changes in adaptive thermogenesis in female and male physique athletes.

Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes during a competition preparation among drug-free physique athletes. The participants were female (10 competing (COMP) and 10 nondieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP were tested before they started their diet 23 weeks before competing (PRE), during their diet one week before competing (MID), and 23 weeks after competing (POST), whereas CTRL were tested at similar intervals but did not diet. Measurements included body composition by dual-energy X-ray absorptiometry, muscle size, and subcutaneous fat thickness (SFA) by ultrasound, REE by indirect calorimetry, circulating ghrelin, leptin T3, and T4 hormone analysis. Fat mass (FM) and SFA decreased in both sexes (p < 0.001), while males (p < 0.001) lost more lean mass (LM) than females (p < 0.05). Weight loss, decreased energy intake, and increased aerobic exercise (p < 0.05) led to decreased LM- and FM-adjusted REE (p < 0.05), reflecting metabolic adaptation. Absolute leptin levels decreased in both sexes (p < 0.001) but more among females (p < 0.001) due to higher baseline leptin levels. These changes occurred with similar decreases in T3 (p < 0.001) and resting heart rate (p < 0.01) in both sexes. CTRL, who were former or upcoming physique athletes, showed no systematic changes in any measured variables. In conclusion, while dieting, female and male physique athletes experience REE and hormonal changes leading to adaptive thermogenesis. However, responses seemed temporary as they returned toward baseline after the recovery phase. ClinicalTrials.gov (NCT04392752).

Dietary Intake, Serum Hormone Concentrations, Amenorrhea and Bone Mineral Density of Physique Athletes and Active Gym Enthusiasts.

As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 in DXA) in female and male PA was ~41.3 and ~37.2, and in GE ~39.4 and ~35.3, respectively. Low EA (LEA) was found in 10% and 26% of female PA and GE, respectively, and in 11% of male GE. In PA, daily protein intake (g/kg body mass) was ~2.9−3.0, whereas carbohydrate and fat intakes were ~3.6−4.3 and ~0.8−1.0, respectively. PA had higher protein and carbohydrate and lower fat intakes than GE (p < 0.05). Estradiol, testosterone, IGF-1, insulin, leptin, TSH, T4, T3, cortisol, or BMD did not differ between PA and GE. Serum IGF-1 and leptin were explained 6% and 7%, respectively, by EA. In non-users of hormonal contraceptives, amenorrhea was found only in PA (27%) and was associated with lower fat percentage, but not EA, BMD, or hormones. In conclusion, off-season dietary intakes, hormone levels, and BMD meet the recommendations in most of the PA and GE. Maintaining too-low body fat during the off-season may predispose to menstrual disturbances.

Age But Not Menopausal Status Is Linked to Lower Resting Energy Expenditure.

CONTEXT: It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). OBJECTIVES: We investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and FSH concentrations explain REEadj in midlife. METHODS: We divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17 to 21, group II (n = 35) of those aged 22 to 38, and group III (n = 59) of those aged 41 to 58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30), or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry, and hormones using immunoassays. RESULTS: The REEadj of group I was 126 kcal/day [95% confidence interval (CI): 93-160] higher than that of group III, and the REEadj of group II was 88 kcal/day (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/day (95% CI: 63-138 kcal/day) higher REEadj than their middle-aged mothers (all P < .001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. CONCLUSIONS: We demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.

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.

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.

The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors.

Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35-50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3-4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35-50% decrease in body fat in previously normal-weight females can recover within 3-4 months of increased energy intake.