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Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.
Stomby, A, Otten, J, Ryberg, M, Andrew, R, Walker, BR, Olsson, T
European journal of endocrinology. 2020;182(4):447-457
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Cushing syndrome is caused by an overexposure to cortisol and associated with abdominal adiposity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM), and therefore bears similarities with metabolic syndrome and obesity. Whilst circulating cortisol levels are normal or slightly decreased in obese individuals, they tend to be increased in T2DM. The aim of this study was to investigate associations between obesity and T2DM measures and glucocorticoid metabolism, and any possible effects of a palaeolithic diet (PD) with or without exercise. In this single-blind study (investigators examining patients were blind to intervention), 28 patients with overweight or obesity and T2DM were randomised to either a PD alone or combined with a structured resistance and aerobic exercise programme for 12 weeks. The PD was based on a high intake of vegetables, fruit, lean meat, nuts, egg, fish and seafood, whilst grains, sugar, salt, dairy products and refined fats were reduced. Body mass index, waist circumference, glycaemic control, liver and systemic insulin sensitivity improved in both groups with no statistically significant difference between groups. There was no association between insulin sensitivity and indices of tissue specific glucocorticoid metabolism. PD with and without exercise was associated with increased conversion of the inactive cortisone to the active cortisol through increased activity of the conversion enzyme in the liver, but not with increased urinary excretion of glucocorticoid metabolites. The authors concluded that the results suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
Abstract
CONTEXT Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. OBJECTIVE Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. DESIGN Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). SETTING Umeå University Hospital. PARTICIPANTS Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. MAIN OUTCOME MEASURES Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. RESULTS Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5β-THF/THE in urine increased in both groups. CONCLUSIONS These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
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A randomized, double blind, placebo controlled, multicenter clinical trial to assess the efficacy and safety of Emblica officinalis extract in patients with dyslipidemia.
Upadya, H, Prabhu, S, Prasad, A, Subramanian, D, Gupta, S, Goel, A
BMC complementary and alternative medicine. 2019;19(1):27
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Emblica officinalis (Amla or Indian gooseberry) is a fruit that has been traditionally used in Ayurvedic medicine. It has been shown to be effective in the management of dyslipidemia (abnormal fat metabolism), a risk factor for heart disease, in animal models and in pilot clinical studies without major side effects. This multicenter, randomised, placebo controlled, double blind clinical trial was designed to evaluate the efficacy and safety of a proprietary full spectrum amla extract (containing pulp and seeds) in patients with dyslipidemia. 98 patients were enrolled and all completed the 12 week study. None of them were taking any medication for their dyslipidaemia. All the patients enrolled in the study were also asked to initiate lifestyle changes (healthy diet with exercise at least 4 days a week). Apart from conventional lipid parameters, the investigators also measured a number of other parameters relevant to heart disease, including the atherogenic index of plasma (AIP, a marker of heart disease risk). Compared to the placebo group the amla group had significantly greater reductions in triglycerides, LDL-cholesterol, VLDL-cholesterol and the atherogenic index of plasma (AIP, a better predictor of heart disease risk). There were no significant changes in HDL-cholesterol, CoQ10 (lowering of CoQ10 is a concern with many cholesterol lowering drugs), homocysteine, thyroid stimulating hormone (TSH) or fasting blood glucose. Four non-serious adverse events were observed: mild headache, mild fever, two times gastritis (all resolved with standard treatment), three were in the placebo group, one in the amla group. There were no changes in routine blood tests and vital signs (blood pressure, heart rate, temperature, respiratory rate). The authors conclude that the amla extract has significant potential to improve dyslipidaemia without side effects commonly seen with cholesterol lowering drugs.
Abstract
BACKGROUND Dyslipidemia is one of the most frequently implicated risk factors for development of atherosclerosis. This study evaluated the efficacy of amla (Emblica officinalis) extract (composed of polyphenols, triterpenoids, oils etc. as found in the fresh wild amla fruit) in patients with dyslipidemia. METHODS A total of 98 dyslipidemic patients were enrolled and divided into amla and placebo groups. Amla extract (500 mg) or a matching placebo capsule was administered twice daily for 12 weeks to the respective group of patients. The patients were followed up for 12 weeks and efficacy of study medication was assessed by analyzing lipid profile. Other parameters evaluated were apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), Coenzyme Q10 (CoQ10), high-sensitive C-reactive protein (hsCRP), fasting blood sugar (FBS), homocysteine and thyroid stimulating hormone (TSH). RESULTS In 12 weeks, the major lipids such as total cholesterol (TC) (p = 0.0003), triglyceride (TG) (p = 0.0003), low density lipoprotein cholesterol (LDL-C) (p = 0.0064) and very low density lipoprotein cholesterol (VLDL-C) (p = 0.0001) were significantly lower in amla group as compared to placebo group. Additionally, a 39% reduction in atherogenic index of the plasma (AIP) (p = 0.0177) was also noted in amla group. The ratio of Apo B to Apo A1 was reduced more (p = 0.0866) in the amla group as compared to the placebo. There was no significant change in CoQ10 level of amla (p = 0.2942) or placebo groups (p = 0.6744). Although there was a general trend of FBS reduction, the numbers of participants who may be classified as pre-diabetes and diabetes groups (FBS > 100 mg/dl) in the amla group were only 8. These results show that the amla extract used in the study is potentially a hypoglycaemic as well. However, this needs reconfirmation in a larger study. CONCLUSIONS The Amla extract has shown significant potential in reducing TC and TG levels as well as lipid ratios, AIP and apoB/apo A-I in dyslipidemic persons and thus has scope to treat general as well as diabetic dyslipidemia. A single agent to reduce cholesterol as well as TG is rare. Cholesterol reduction is achieved without concomitant reduction of Co Q10, in contrast to what is observed with statins. TRIAL REGISTRATION Registered with Clinical Trials Registry- India at www.ctri.nic.in (Registration number: CTRI/2015/04/005682 ) on 8 April 2015 (retrospectively registered).
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Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis.
Uusitupa, M, Khan, TA, Viguiliouk, E, Kahleova, H, Rivellese, AA, Hermansen, K, Pfeiffer, A, Thanopoulou, A, Salas-Salvadó, J, Schwab, U, et al
Nutrients. 2019;11(11)
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With Type 2 Diabetes growing globally this paper analyses whether T2D is preventable with lifestyle measures including diet. Seven RCTs were included for review with a total of 4090 participants, and 2466 incidents of T2D, and were chosen on the basis that the lifestyle interventions included both physical exercise and diet (typically Mediterranean Diet). They found that diet and lifestyle intervention reduced the risk of T2D by 47%. Sustained risk reduction was also found in follow-up studies up to 10 years later with participants maintaining improved blood glucose control. Lifestyle interventions may also reduce risk factors for cardiovascular disease. Weight reduction was considered a cornerstone of preventing T2D and adherence to lifestyle changes a key element in long term prevention. Dietary foods reviewed include processed meats, white rice and sugars which correlated highly with T2D whilst leafy greens, berries, wholegrains, legumes, dietary fibre and yoghurt correlate with a lower risk of T2D. Dietary patterns of skipping breakfast and snacking correlate higher with T2D. Different criteria for evaluating physical activity estimate that it reduces risk factors by 50%. In conclusion there is high evidence that lifestyle factors which optimise diet, increase physical activity and promote weight reduction are preventative factors for T2D and can be sustained long term.
Abstract
Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.
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Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women.
Ilich, JZ, Kelly, OJ, Liu, PY, Shin, H, Kim, Y, Chi, Y, Wickrama, KKAS, Colic-Baric, I
Nutrients. 2019;11(5)
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A woman’s menopausal years are believed to bring about weight gain due to various biological mechanisms, such as depletion of oestrogen. Many women undertake weight loss diets, in an attempt to control the weight gain, and although weight loss can reduce the risk factors for metabolic and cardiovascular disease etc, it can also lead to accelerated loss bone density and muscle mass. The objective of this study was to investigate whether by complementing a low-calorie diet with 4 to 5 servings of low-fat dairy foods per day and/or supplementing with calcium and vitamin D supplements would aid weight loss and preserve either/both bone and muscle mass. The study was conducted on 189 early postmenopausal, obese women. It was a randomized, placebo-controlled clinical trial conducted over 6 months. Researchers found that results were better for the participants on the low-fat dairy foods and those supplementing with calcium and vitamin D when compared to the placebo group (who only had placebo pills). They suggest that when embarking on a weight loss program it is beneficial to include 4 to 5 servings of low-fat dairy foods each day and take calcium and vitamin D supplements will have a positive impact on weight loss, bone density and muscle mass in post-menopausal women.
Abstract
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
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Effects of n-3 fatty acids and exercise on oxidative stress parameters in type 2 diabetic: a randomized clinical trial.
Fayh, APT, Borges, K, Cunha, GS, Krause, M, Rocha, R, de Bittencourt, PIH, Moreira, JCF, Friedman, R, da Silva Rossato, J, Fernandes, JR, et al
Journal of the International Society of Sports Nutrition. 2018;15:18
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An elevated blood glucose level is one of the key metabolic abnormalities associated with complications in type 2 diabetes. Literature shows that individuals with type 2 diabetes have higher inflammatory levels than those with normal blood glucose tolerance. The aim of this study was to examine if omega-3 polyunsaturated fatty acid (PUFA) supplementation can reduce the inflammatory response associated with high-intensity exercise in type 2 diabetic individuals. This was a randomised, double-blind controlled study, which recruited 30 type 2 diabetic men and women aged between 30 and 60 years. Results indicate that after 8 weeks, omega-3 PUFA supplementation diminished the concentration of the total reactive antioxidant potential and triglyceride levels after high intensity exercise, however did not reduce the inflammatory response.
Abstract
BACKGROUND The relationship between diabetes and oxidative stress has been previously reported. Exercise represents a useful non-pharmacological strategy for the treatment in type 2 diabetic (T2DM) patients, but high intensity exercise can induce a transient inflammatory state and increase oxidative stress. Nutritional strategies that may contribute to the reduction of oxidative stress induced by acute exercise are necessary. The aim of this study was to examine if n-3 PUFA supplementation intervention can attenuate the inflammatory response and oxidative stress associated with high intensity exercise in this population. As a primary outcome, lipoperoxidation measurements (TBARS and F2-isoprostanes) were selected. METHODS Thirty T2DM patients, without chronic complications, were randomly allocated into two groups: placebo (gelatin capsules) or n-3 PUFA (capsules containing 180 mg of eicosapentaenoic acid and 120 mg of docosahexaenoic acid). Blood samples were collected fasting before and after 8 weeks supplementation. In the beginning and at the end of protocol, an acute exercise was performed (treadmill), and new blood samples were collected before and immediately after the exercise for measurements of oxidative stress and high-sensitivity C-reactive protein (hs-CRP). RESULTS After the supplementation period, a decrease in triglycerides levels was observed only in n-3 PUFA supplementation group (mean difference and 95% CI of 0.002 (0.000-0.004), p = 0.005). Supplementation also significantly reduced TRAP levels after exercise (mean difference and 95% CI to 9641 (- 20,068-39,351) for - 33,884 (- 56,976 - -10,793), p = 0.004, Cohen's d effect size = 1.12), but no significant difference was observed in n-3 PUFA supplementation group in lipoperoxidation parameters as TBARS (mean difference and 95% CI to - 3.8 (- 10-2.4) for - 2.9 (- 1.6-7.4) or F2-isoprostanes (mean difference and 95% CI -0.05 (- 0.19-0.10) for - 0.02 (- 0.19-0.16), p > 0.05 for both. CONCLUSION PUFA n-3 supplementation reduced triglycerides as well as TRAP levels after exercise, without a significant effect on inflammatory and oxidative stress markers.This study is registered at ClinicalTrials.gov with the registration number of NCT03182712.
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The Association between Breakfast Skipping and Body Weight, Nutrient Intake, and Metabolic Measures among Participants with Metabolic Syndrome.
Zhang, L, Cordeiro, LS, Liu, J, Ma, Y
Nutrients. 2017;9(4)
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There is conflicting evidence on the benefits of either skipping breakfast versus the idea that breakfast is the most important meal of the day. This study examines the effects of skipping breakfast on weight loss in a group of 240 participants diagnosed as having Metabolic syndrome (MetS). The study looked at data from a diet trial looking at the effects of a high fibre diet or the American Heart Association diet on MetS, in which they all also monitored breakfast eating patterns, to see if there was any change to body weight, nutrient intakes, and selected metabolic measures. The study lasted one year, and dietary recalls were collected throughout. The results showed that at the start of the trial 32.9% of the participants self-reported regularly skipped breakfast and generally they had lower levels of vitamins B1, B3 and folate intake. They also had a higher fat intake compared to those who ate breakfast. However, at the end of the year there was no statistical differences between those who ate and those who skipped breakfast when it came to the other metabolic parameters of weight, BMI, weight circumference, blood pressure, cholesterol, and fasting glucose. Interestingly at the end of the trial only 14% reported skipping breakfast suggesting that participants had the intention to change their eating patterns because of having participated in the trial. The study concluded that skipping breakfast alone was not enough to influence MetS.
Abstract
The effect of skipping breakfast on health, especially in adults, remains a controversial topic. A secondary data analysis was conducted to examine associations between breakfast eating patterns and weight loss, nutrient intake, and metabolic parameters among participants with metabolic syndrome (MetS) (n = 240). Three randomly selected 24-h dietary recalls were collected from each participant at baseline and at the one-year visit. Skipped breakfast was seen in 32.9% at baseline and in 17.4% at the one-year visit, respectively. At baseline, after adjustment for demographics and physical activity, participants who ate breakfast had a higher thiamin, niacin, and folate intake than did breakfast skippers (p < 0.05); other selected parameters including body weight, dietary quality scores, nutrient intake, and metabolic parameters showed no significant differences between the two groups (p ≥ 0.05). From baseline to one year, after adjustment for covariates, mean fat intake increased by 2.7% (95% confidence intervals (CI): -1.0, 6.5%) of total energy in breakfast skippers in comparison to the 1.2% decrease observed in breakfast eaters (95% CI: -3.4, 1.1%) (p = 0.02). Mean changes in other selected parameters showed no significant differences between breakfast skippers and eaters (p > 0.05). This study did not support the hypothesis that skipping breakfast has impact on body weight, nutrient intakes, and selected metabolic measures in participants with MetS.
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Effect of protein and carbohydrate solutions on running performance and cognitive function in female recreational runners.
Gui, Z, Sun, F, Si, G, Chen, Y
PloS one. 2017;12(10):e0185982
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Research has shown that consuming a carbohydrate-electrolyte solution (CES) during endurance exercise can improve performance, delay fatigue and ameliorate post-exercise cognitive dysfuction when compared with a noncaloric placebo (PLA). The addition of protein to the CES (CPES) has been suggested to increase these benefits however the current data is limited. The aim of this crossover study was to investigate whether the added protein to a CES would improve exercise performance and cognitive function in 11 female recreational marathon runners. Participants were randomised to consume one of the three solutions (CES, CPES or PLA) every 2.5km during a 21km run, with a 28-day interval, and their VO2max and cognitive function were recorded after the run. This study showed that CES improved endurance performance compared with PLA, however adding protein to the CES did not provide any additional performance benefit. The CPES solution did benefit visual motor speed compared to PLA, but no differences were found in the other cognitive function tests.
Abstract
This study compared the effects of a carbohydrate-electrolyte-protein solution (CEPS, 2% protein plus 4% carbohydrate), carbohydrate-electrolyte solution (CES, 6% carbohydrate), and noncaloric sweetened placebo (PLA) on both 21-km running performance and cognitive function. Eleven female recreational endurance runners performed a 21-km time-trial running on three occasions, separated by at least 28 days. In a randomized cross-over design, they ingested CEPS, CES, or PLA at a rate of 150 mL every 2.5 km with no time feedback. A cognitive function test was performed before and after the run. Participants ingested approximately 24 g/h carbohydrate plus 12 g/h protein in CEPS trial, and 36 g/h carbohydrate in CES trial during each 21-km trial. Time to complete the time-trial was slightly shorter (P < 0.05) during CES (129.6 ± 8.8 min) than PLA (134.6 ± 11.5 min), with no differences between CEPS and the other two trials. The CEPS trial showed higher composite of visual motor speed than the PLA trial (P < 0.05). In conclusion, CES feedings might improve 21-km time-trial performance in female recreational runners compared with a PLA. However, adding protein to the CES provided no additional time-trial performance benefit. CEPS feeding during prolonged exercise could benefit visual motor speed compared to PLA alone, but no differences in the performance of the other cognitive function tests were found.
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Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.
Karl, JP, Smith, TJ, Wilson, MA, Bukhari, AS, Pasiakos, SM, McClung, HL, McClung, JP, Lieberman, HR
Metabolism: clinical and experimental. 2016;65(4):416-27
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Intermittent periods of substantial energy deficit, common among military personnel, result in multiple endocrine and metabolic signals. To date, the association between metabolic and endocrine markers with appetite regulation remain controversial. Using a novel model, the aim of this crossover study was to determine the effects of severe energy deprivation on cognitive function, and explore the metabolic response and its impact on appetite regulation in 23 young adults. Following prescribed exercise, participants were randomised to consume an energy balanced or energy deficit diet. The findings of this study showed that during energy deprivation, metabolic homeostasis modulates appetite independent of diet volume. Though further studies are required, these results suggest that metabolic and endocrine signals are associated with adipose and lean tissue loss to restore energy balance.
Abstract
BACKGROUND Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. METHODS Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. RESULTS Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No associations between physiologic variables measured during EB and ad libitum energy intake following EB were observed. However, serum leptin and net protein balance measured during ED were inversely associated with ad libitum energy intake following ED (R(2)=0.48, P=0.01). CONCLUSION These findings suggest that changes in metabolic homeostasis during energy deprivation modulate appetite independent of reductions in diet volume. Following energy deprivation, physiologic signals of adipose and lean tissue loss may drive restoration of energy balance. CLINICAL TRIALS REGISTRATION www.clinicaltrials.gov #NCT01603550.
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The fall in leptin concentration is a major determinant of the metabolic adaptation induced by caloric restriction independently of the changes in leptin circadian rhythms.
Lecoultre, V, Ravussin, E, Redman, LM
The Journal of clinical endocrinology and metabolism. 2011;96(9):E1512-6
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Weight loss induced by caloric restriction (CR) is associated with a drop in energy expenditure (EE) beyond that expected for the changes in body composition, often blunting weight loss and predisposing individuals to weight regain. Recent evidence has identified leptin to be associated with this exaggerated decrease in EE. The aim of this trial was to explore the changes in leptin over a 24-hour period in response to caloric restriction, and explore its association with metabolic adaptation. Forty-eight participants were assigned to one of four groups for six months: control, CR, CR with exercise and a low calorie diet. This study indicates that the decline in 24-hour leptin in response to CR is a significant determinant of metabolic adaptation. Based on this study, the authors conclude that this decrease in leptin may underlie the additional reduction in EE observed in individuals following diet-induced weight loss.
Abstract
CONTEXT Leptin is involved in the hormonal regulation of the reproductive, somatotropic, thyroid, and autonomic axes and ultimately in the regulation of energy balance. In parallel to the metabolic adaptation observed in response to caloric restriction (CR), plasma leptin concentrations are substantially decreased, suggesting a role for this hormone in the drop in energy expenditure beyond that predicted by the changes in body composition (metabolic adaptation). AIM: The aim of the study was to explore the changes in 24-h leptin circadian rhythm in response to CR and to investigate the relationship between these changes and metabolic adaptation. DESIGN In a randomized, controlled trial (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy), 48 subjects were assigned to a control group or one of three CR groups for 6 months. Leptin concentration was assessed every 30 min for 24 h, and leptin circadian variations were fitted by Cosinor analysis. Sedentary energy expenditure and urinary catecholamine excretion were measured for 24 h in a metabolic chamber. RESULTS Six months of CR decreased body weight by -11.4 ± 0.6% (mean ± sem; P < 0.001). Mean 24-h circulating leptin concentration decreased by -44 ± 3% (P < 0.001), whereas leptin diurnal amplitude slightly increased over the 6 months of CR. CR caused a metabolic adaptation of -126 ± 25 kcal/d (P <0.001) and a significant decrease in urinary norepinephrine (-13 ± 3%) and T(3) concentrations (10 ± 2%). The metabolic adaptation was significantly and independently related to the changes in 24-h leptin (r(2) = 0 .22, P < 0.01) but not to the changes in leptin amplitude. CONCLUSION Our results confirm an important role for leptin as an independent determinant of the metabolic adaptation in response to CR.