Informing Nature-based Climate Solutions for the United States with the best-available science.

Nature-based Climate Solutions (NbCS) are managed alterations to ecosystems designed to increase carbon sequestration or reduce greenhouse gas emissions. While they have growing public and private support, the realizable benefits and unintended consequences of NbCS are not well understood. At regional scales where policy decisions are often made, NbCS benefits are estimated from soil and tree survey data that can miss important carbon sources and sinks within an ecosystem, and do not reveal the biophysical impacts of NbCS for local water and energy cycles. The only direct observations of ecosystem-scale carbon fluxes, for example, by eddy covariance flux towers, have not yet been systematically assessed for what they can tell us about NbCS potentials, and state-of-the-art remote sensing products and land-surface models are not yet being widely used to inform NbCS policymaking or implementation. As a result, there is a critical mismatch between the point- and tree-scale data most often used to assess NbCS benefits and impacts, the ecosystem and landscape scales where NbCS projects are implemented, and the regional to continental scales most relevant to policymaking. Here, we propose a research agenda to confront these gaps using data and tools that have long been used to understand the mechanisms driving ecosystem carbon and energy cycling, but have not yet been widely applied to NbCS. We outline steps for creating robust NbCS assessments at both local to regional scales that are informed by ecosystem-scale observations, and which consider concurrent biophysical impacts, future climate feedbacks, and the need for equitable and inclusive NbCS implementation strategies. We contend that these research goals can largely be accomplished by shifting the scales at which pre-existing tools are applied and blended together, although we also highlight some opportunities for more radical shifts in approach.

Drivers of Decadal Carbon Fluxes Across Temperate Ecosystems.

Long-running eddy covariance flux towers provide insights into how the terrestrial carbon cycle operates over multiple timescales. Here, we evaluated variation in net ecosystem exchange (NEE) of carbon dioxide (CO2) across the Chequamegon Ecosystem-Atmosphere Study AmeriFlux core site cluster in the upper Great Lakes region of the USA from 1997 to 2020. The tower network included two mature hardwood forests with differing management regimes (US-WCr and US-Syv), two fen wetlands with varying levels of canopy sheltering and vegetation (US-Los and US-ALQ), and a very tall (400 m) landscape-level tower (US-PFa). Together, they provided over 70 site-years of observations. The 19-tower Chequamegon Heterogenous Ecosystem Energy-balance Study Enabled by a High-density Extensive Array of Detectors 2019 campaign centered around US-PFa provided additional information on the spatial variation of NEE. Decadal variability was present in all long-term sites, but cross-site coherence in interannual NEE in the earlier part of the record became weaker with time as non-climatic factors such as local disturbances likely dominated flux time series. Average decadal NEE at the tall tower transitioned from carbon source to sink to near neutral over 24 years. Respiration had a greater effect than photosynthesis on driving variations in NEE at all sites. Declining snowfall offset potential increases in assimilation from warmer springs, as less-insulated soils delayed start of spring green-up. Higher CO2 increased maximum net assimilation parameters but not total gross primary productivity. Stand-scale sites were larger net sinks than the landscape tower. Clustered, long-term carbon flux observations provide value for understanding the diverse links between carbon and climate and the challenges of upscaling these responses across space.

Vapor pressure deficit helps explain biogenic volatile organic compound fluxes from the forest floor and canopy of a temperate deciduous forest.

Biogenic volatile organic compounds (BVOCs) play critical roles in ecological and earth-system processes. Ecosystem BVOC models rarely include soil and litter fluxes and their accuracy is often challenged by BVOC dynamics during periods of rapid ecosystem change like spring leaf out. We measured BVOC concentrations within the air space of a mixed deciduous forest and used a hybrid Lagrangian/Eulerian canopy transport model to estimate BVOC flux from the forest floor, canopy, and whole ecosystem during spring. Canopy flux measurements were dominated by a large methanol source and small isoprene source during the leaf-out period, consistent with past measurements of leaf ontogeny and theory, and indicative of a BVOC flux situation rarely used in emissions model testing. The contribution of the forest floor to whole-ecosystem BVOC flux is conditional on the compound of interest and is often non-trivial. We created linear models of forest floor, canopy, and whole-ecosystem flux for each study compound and used information criteria-based model selection to find the simplest model with the best fit. Most published BVOC flux models do not include vapor pressure deficit (VPD), but it entered the best canopy, forest floor, and whole-ecosystem BVOC flux model more than any other study variable in the present study. Since VPD is predicted to increase in the future, future studies should investigate how it contributes to BVOC flux through biophysical mechanisms like evaporative demand, leaf temperature and stomatal function.

Effectiveness and Feasibility of a Remote Lifestyle Intervention by Dietitians for Overweight and Obese Adults: Pilot Study.

BACKGROUND: To tackle the problem of obesity and related diseases in Switzerland, cost-efficient, effective, and innovative primary health care interventions for weight management are required. In this context, Oviva has developed a scalable technology for registered dietitians to counsel overweight and obese patients via a mobile phone app. OBJECTIVE: The aim of this study was to evaluate the effectiveness and feasibility of weight loss counseling by dietitians using a mobile phone app for patients with overweight and obesity. METHODS: In this pre- and posttest pilot study, overweight and obese adults participated in a 1-year behavioral intervention to lose weight through remote counseling by dietitians in the German-speaking part of Switzerland. The study started in April 2016 and finished in May 2018. Participants received individual counseling through the app and the exchange with the dietitian focused on regular feedback on photo-based food log, motivation, and education. The contents were tailored to the individual lifestyle goal set. The predefined intensity of remote counseling decreased during the year. Group chat could be used. The outcomes examined were changes in weight (primary outcome), hemoglobin A1c, fasting glucose, fasting insulin, triglyceride, high-density lipoprotein cholesterol, blood pressure (BP), body mass index (BMI), waist circumference, body fat, and responses to a self-administered questionnaire with questions regarding participants' physical activity, dietary assessment, and health-related quality of life. Changes were tested at baseline, after 3 months, and after 12 months, as well as between the third and the 12th month. RESULTS: In total, 36 women and 7 men, with a mean age of 40.6 years, participated and 36 participants completed the study. Median weight change after the first 12 weeks was -3.8 kg (range: -15 to 2.4 and P<.001), between week 12 and week 52 it was -1.1 kg (range: -9.7 to 7 and P=.08), and the median change during the entire period of intervention was -4.9 kg (range: -21.9 to 7.5 and P<.001). Furthermore, changes in BMI, waist circumference, body fat, and BP between baseline and 12 weeks and between baseline and 52 weeks were also significant. Significant changes in certain eating habits were also demonstrated (higher frequency of vegetable, fruit, and breakfast consumption and lower frequency of alcohol, sweet, and fat consumption). CONCLUSIONS: In addition to the professional skills of a dietitian, a profession-specific app such as Oviva can provide effective support that meets the needs of dietitians and clients on the long path of behavioral change and sustainable weight reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02694614; https://clinicaltrials.gov/ct2/show/NCT02694614 (Archived by WebCite at http://www.webcitation.org/76gYkGOIc).

Physical contact between mesenchymal stem cells and endothelial precursors induces distinct signatures with relevance to the very early phase of regeneration.

Multipotent adult stem cells/precursor cells, especially of the mesenchymal and endothelial lineage, may have great potential for bone tissue engineering. Although their potential is highly recognized, not much is known about the underlying molecular mechanisms that initiate the regeneration process, connect osteogenesis, and angiogenesis and, finally, orchestrate renewal of bone tissue. Our study addressed these questions by generating two in vitro cell culture models to examine the changes in the global gene expression patterns of endothelial precursor cells and mesenchymal stem cells after 24 hours of either humoral (conditioned medium) or direct cell-cell interaction (co-culture). Endothelial precursor cells were isolated from human buffy coat and mesenchymal stem cells from the bone marrow of the femoral head. The comparison of the treated and control cells by microarray analyses revealed in total more than 1500 regulated genes, which were analyzed for their affiliation to angiogenesis and osteogenesis. Expression array analyses at the RNA and protein level revealed data with respect to regulated genes, pathways and targets that may represent a valid basis for further dissection of the systems biology of regeneration processes. It may also be helpful for the reconstitution of the natural composition of a regenerative microenvironment when targeting tissue regeneration both in vitro and in situ.

Moderate dietary weight loss reduces myocardial steatosis in obese and overweight women.

BACKGROUND: Excessive myocardial triglyceride (MTG) content in obesity and type 2 diabetes is associated with impaired cardiac function. Previous studies suggest that MTG could be mobilized through lifestyle interventions. We assessed influences of moderate dietary weight loss in non diabetic obese and overweight women on MTG content and cardiac function. METHODS: We selected a subgroup of 38 women from the B-SMART study population. The B-SMART study compared weight loss and associated metabolic and cardiovascular markers with reduced-carbohydrate and reduced-fat hypocaloric diets. Selected subjects had completed a cardiac magnetic resonance (MR) scan including imaging and proton spectroscopy to assess cardiac structure and function as well as MTG content. RESULTS: An average weight reduction of 5.4 ± 4.3 kg at six months was associated with a relative decrease of MTG of 25% (from 0.72 ± 0.29% at baseline to 0.54 ± 0.23% at follow-up, p<0.001). The response was similar with carbohydrate and fat restriction. Diastolic function expressed as ratio of peak filling rate in E- and A-Phase (PFRE/PFRA) was unchanged. Reductions of left atrial size (from 21.9 ± 4.0 cm(2) to 20.0 ± 3.7 cm(2), p=0.002), the normalized ratio of PFRE and early diastolic lengthening velocity PLV (from 8.2 ± 2.6 to 7.5 ± 2.5, p<0.001) and fat free mass (from 55.1 ± 6.9 kg to 52.7 ± 6.5 kg, p=0.007) reflected altered cardiac volume loading after diet, but did not correlate to MTG content. CONCLUSIONS: Moderate dietary weight loss significantly reduced MTG content in women with uncomplicated overweight or obesity. Macronutrient composition of the diet did not significantly affect the extent of MTG reduction.

Left ventricular mass and function with reduced-fat or reduced-carbohydrate hypocaloric diets in overweight and obese subjects.

In animals, carbohydrate and fat composition during dietary interventions influenced cardiac metabolism, structure, and function. Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity, we investigated whether these interventions differentially affect left ventricular mass, cardiac function, and blood pressure. We randomized 170 overweight and obese subjects (body mass index, 32.9±4.4; range, 26.5-45.4 kg/m(2)) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake. We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months. Ninety subjects completing the intervention period had a full cardiac MRI data set. Subjects lost 7.3±4.0 kg (7.9±3.8%) with reduced-carbohydrate diet and 6.2±4.2 kg (6.7±4.4%) with reduced-fat diet (P<0.001 within each group; P=not significant between interventions). Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets (5.4±5.4 g) or low-fat diets (5.2±4.8 g; P<0.001 within each group; P=not significant between interventions). Systolic and diastolic left ventricular function did not change with either diet. The 24-hour systolic blood pressure decreased similarly with both interventions. Body weight change (ß=0.33; P=0.02) and percentage of ingested n-3 polyunsaturated fatty acids (ß=-0.27; P=0.03) predicted changes in left ventricular mass. In conclusion, weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period. However, n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass.

Safety and efficacy of everolimus after kidney and hematopoietic stem cell transplantation.

BACKGROUND: The aim of this retrospective study was to investigate the efficacy of everolimus at our institution and to report incidence and type of side effects in patients who underwent kidney transplantation or hematopoietic stem cell transplantation (HSCT). MATERIAL/METHODS: Electronic medical records were evaluated for 122 patients (76 men and 46 women) treated with everolimus between January 2000 and January 2009. Of these patients, 81 had undergone kidney transplantation (mean age: 56±12 years) and 41 patients were treated with HSCT (mean age: 47±11 years). RESULTS: Everolimus was discontinued in a total of 53% of patients (n=64) with no difference observed in kidney transplant recipients vs. stem cell transplanted patients (p=0.85). In one half of the patients, cessation of the drug was due to a lack of long-term efficacy (n=32). In the other half, everolimus was discontinued due to side effects (n=32). However, patients with side effects had no elevated everolimus concentrations (5.5±2.3 vs. 5.2±1.7 ng/ml; p=0.39). Pneumonitis (n=5) or proteinuria over 1.5 g per day (n=13) were only observed in kidney transplant patients, while polyomavirus-induced cystitis (n=3) and thrombotic thrombocytopenic purpura (n=7) were only observed in stem cell transplanted patients. CONCLUSIONS: Everolimus was an effective immunosuppressive agent in half of the patients. A quarter of all patients developed side effects resulting in discontinuation of the drug. The profile of side effects in kidney recipients clearly differs from hematopoietic stem cell transplanted patients.

Myocardial steatosis, cardiac remodelling and fitness in insulin-sensitive and insulin-resistant obese women.

BACKGROUND: Obesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is associated with myocardial triglyceride (MTG) accumulation. Lipotoxic injury from altered myocardial metabolism may be causative. Whether such association also exists in obese, non-diabetic women is unknown. OBJECTIVE: To explore the relation between MTG content, cardiac remodelling and cardiorespiratory fitness in obese, insulin-sensitive and insulin-resistant non-diabetic women. DESIGN: Cross-sectional investigation. SETTING: Academic clinical research centre. PATIENTS: 65 Overweight/obese and sedentary, but otherwise healthy women (body mass index 33±4 kg/m(2); age 45±10 years). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Cardiac structure and function measured by cardiovascular magnetic resonance imaging and MTG content of the interventricular septum by (1)H MR spectroscopy. Additional outcomes were cardiopulmonary fitness and insulin sensitivity during oral glucose tolerance testing. RESULTS: Insulin resistance (composite insulin sensitivity index (C-ISI) <4.6) was present in 29 women. MTG content was higher (0.83±0.30 vs 0.61±0.23, p=0.002) and left ventricular diastolic (p<0.01), but not systolic function was reduced in women with insulin resistance compared with insulin-sensitive women. The remodelling index defined as left ventricular mass divided by end-diastolic volume was increased in women with impaired glucose tolerance (p=0.006). Furthermore, cardiopulmonary fitness was equal in both groups, but was inversely correlated with MTG (r=-0.28, p=0.02). CONCLUSIONS: In overweight and obese women, insulin resistance is associated with increased MTG content, cardiac remodelling and reduced diastolic function. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00956566.

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

UNLABELLED: Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. CONCLUSION: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet.

Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content.

OBJECTIVE: Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. RESEARCH DESIGN AND METHODS: We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 +/- 8.9 years, BMI 33.8 +/- 4 kg/m(2)). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test. RESULTS: For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = -0.27, P < 0.05), and visceral (r = -0.25, P < 0.05) and total fat mass (r = -0.32, P < 0.05), but not to intramyocellular lipids (r = -0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r(2) = -0.43, P < 0.01, r(2) = -0.34, and r(2) = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. CONCLUSIONS: Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction.

Influences of normobaric hypoxia training on physical fitness and metabolic risk markers in overweight to obese subjects.

Previous studies suggested that hypoxia and exercise may have a synergistic effect on cardiovascular and metabolic risk factors. We conducted a single blind study in overweight to obese subjects to test the hypothesis that training under hypoxia (HG, n = 24, FiO(2) = 15%) results in similar or even greater improvement in body weight and metabolic risk markers compared with exercise under normoxia (NG, n = 21, FiO(2) = 21%). After an initial metabolic evaluation including incremental exercise testing, subjects trained in normoxic or hypoxic conditions thrice weekly over a 4-week period at a heart rate corresponding to 65% of maximum oxygen uptake (VO(2max)). The experimental groups were similar at the start of the investigation and weight stable during the training period. Subjects in the hypoxia group trained at a significantly lower workload (P < 0.05). Yet, both groups showed similar improvements in VO(2max) and time to exhaustion. Respiratory quotient and lactate at the anaerobic threshold as well as body composition improved more in the hypoxia group. We conclude that in obese subjects, training in hypoxia elicits a similar or even better response in terms of physical fitness, metabolic risk markers, and body composition at a lower workload. The fact that workload and, therefore, mechanic strain can be reduced in hypoxia could be particularly beneficial in obese patients with orthopedic comorbidities.

Genetic variant in HK1 is associated with a proanemic state and A1C but not other glycemic control-related traits.

OBJECTIVE: A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice. RESEARCH DESIGN AND METHODS: The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control-related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients. RESULTS: Our study confirms a strong association between the rs7072268-T allele and increased A1C (beta = 0.029%; P = 2.22 x 10(-7)). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT-related parameters, n = 18,694). In contrast, rs7072268-T allele decreases hemoglobin levels (n = 13,416; beta = -0.054 g/dl; P = 3.74 x 10(-6)) and hematocrit (n = 11,492; beta = -0.13%; P = 2.26 x 10(-4)), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018). CONCLUSIONS: HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia is a frequent complication of the diabetes state.

Influences of normobaric hypoxia training on metabolic risk markers in human subjects.

PURPOSE: Endurance exercise and hypoxia regulate pathways that are crucial to glucose and lipid metabolism. We hypothesized that training under hypoxia results in similar or even greater metabolic improvement compared with exercise under normoxia at a lower workload. METHODS: We randomly assigned 20 healthy men to single blind training under hypoxia (FiO2 = 15%) or normoxia (FiO2 = 21%). Subjects trained thrice weekly for 60 min over a 4-wk period at a heart rate measured at 3 mmol x L(-1) lactate during pretraining exercise testing. Before and after the training period, we determined body composition, venous blood parameters, oral glucose tolerance, and blood pressure. Furthermore, we assessed oxygen uptake (VO2), lactate, and respiratory quotient, and heart rate (HR) during incremental exercise testing, both in hypoxia and in normoxia. Training workload was 1.39 +/- 0.2 W x kg(-1) in the hypoxia and 1.67 +/- 0.15 W x kg(-1) in the normoxia group (P< 0.001) with an identical training heart rate in both groups. RESULTS: Exercise capacity improved similarly with both interventions. With hypoxia training, body fat content, triglycerides, HOMA-Index, fasting insulin (P < 0.05), and area under the curve for insulin (P < 0.01) during the oral glucose tolerance test improved more than with the training in normoxia. We did not observe major changes in adipokine measurements. CONCLUSION: Endurance training in hypoxia over a 4-wk period elicits a similar or even better response in terms of cardiovascular and metabolic risk factors than endurance exercise in normoxia. The fact that workload and, therefore, mechanic strain can be reduced in hypoxia could be particularly beneficial in obese patients and in patients with orthopedic conditions.

Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment.

CONTEXT: The serotonin and norepinephrine transporter inhibitor sibutramine is a widely used antiobesity drug. In acute studies, the peripheral sympathomimetic effect of sibutramine was counteracted by a central sympatholytic action. OBJECTIVE: The objective was to test the hypothesis that blood pressure responses to long-term sibutramine therapy may be related to sympathetic nerve traffic before treatment in a prospective open-label study in an academic clinical research center. PATIENTS: This study comprised 20 obese subjects (body mass index, 30-40 kg/m2; age, 30-57 yr) receiving 5 d of placebo treatment followed by open-label 15 mg/d sibutramine and hypocaloric diet over 12 wk. MAIN OUTCOME MEASURES: Body weight, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) (microneurography), plasma catecholamines, and adipose tissue gene expression were measured. RESULTS: Open-label sibutramine treatment decreased body weight 4.1 kg (P<0.01) and MSNA 17 bursts per minute (P=0.001), and increased diastolic blood pressure 3 mm Hg (P<0.05) and heart rate 8 bpm (P<0.01). The change in blood pressure with sibutramine treatment was inversely correlated with initial MSNA (r2=0.34; P<0.01). Chronic sibutramine treatment increased adrenoreceptor gene expression and plasma catecholamines. CONCLUSIONS: The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment.