Absence Of Caloric Restriction Research Articles

The effect of LCn-3 PUFA supplementation on body weight, body composition, and muscle function during alternate-day fasting (ADF)

During weight loss the loss of body mass is associated not only with body fat reduction but also with a decrease in fat-free mass (FFM), related to the reduction in muscle mass and function(1). Supplementation with long-chain n-3 fatty acids (LCn-3 PUFA), in the absence of caloric restriction, results in a significant decrease in fat mass and an increase in FFM(2) along with improvements in muscle mass and strength(3). However, the impact of supplementation with LCn-3 PUFA during weight loss) remains unknown. Therefore, the aim of this study was to explore the effects of LCn-3 PUFA supplementation, in the form of Krill oil (KO), during alternate day fasting (ADF) on body weight, fat mass loss, FFM and muscle function changes in healthy overweight and obese adults.A total of 41 men and women (age: 39.35 ± 10.4 years, BMI: 31.05 ± 4.2 kg/m2) completed the study (NCT06001632), in which they were randomised into either a KO or Placebo (PL) groups. Both groups carried out 8-weeks of ADF combined with intake of 4 g/day of the corresponding supplements. ADF involved consuming no more than 500 calories on the 'fast day’ and consuming food ad libitum on each 'feed day’. Data on body weight and body composition (TBF-300, Tanita, Manchester, UK), handgrip strength (Handheld Hydraulic Dynamometer, Vernier Jamar; England, UK), and time to conduct 5 repetition of chair rising test were obtained pre-and post-intervention. Changes from baseline within groups were assessed using paired samples t-test. Mixed analysis of variance (Mixed-ANOVA) was used to measure 2-way interactions between time and group to identify the differences between groups. All statistical analysis were conducted using IBM Statistical Package for the Social Sciences SPSS 28.0.In both groups, body mass decreased significantly (KO:-4.7 ± 0.4kg, p<0.001; PL:-4.5 ± 0.4kg, p<0.001), along with a significant reduction in fat mass (KO:-2.4 ± 0.5kg p<0.001; PL:-2.3 ± 0.5kg p<0.001), and FFM (KO:-0.6 ± 0.2kg p<0.001; PL:-0.7 ± 0.2kg, p<0.001), with no differences between groups. In the PL group, there was a reduction in handgrip strength (-0.9 ± 0.7 kg, p<0.001), while there was no change in KO group (-0.2 ± 0.5 kg, p=0.1), with a significant difference between groups (p<0.001). In the KO group there was a significant reduction in time to conduct chair rising test (-1.8 ± 0.9s, p<0.05), with no change in the PL group (-0.3 ± 1.3s, p=0.2), with a significant difference between groups (p<0.001).Supplementation with LCn-3 PUFA (4 g/day) during 8 weeks of ADF, applied to individuals living with overweigh and obesity, does not facilitate body or fat mass loss and does not diminish the reduction in FFM. However, it attenuated the reduction in muscle function in healthy overweight and obese adults.

The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment.

Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity. Mice aged 4 weeks were allowed to acclimate for 2 weeks prior to being assigned (N=60/group). Prior to lights off daily (12:12 cycle), animals were fed a ghrelin agonist pill (LY444711; Eli Lilly) or a placebo control (Ctrl) until death. Treatment (GhrAg) animals were pair-fed daily based on the group mean food intake consumed by Ctrl (ad libitum feeding) the prior week. Results indicate an increased lifespan effect (log-rank p=0.0032) for GhrAg versus placebo Ctrl, which weighed significantly more than GhrAg (adjusted for baseline weight). Further studies are needed to determine the full scope of effects of this ghrelin agonist, either directly via increased ghrelin receptor signaling or indirectly via other hypothalamic, systemic, or tissue-specific mechanisms.

Effect of caloric restriction on alveolar bone loss in rats

AimsRecent research suggests an association between longevity, caloric restriction (CR) and reduction of chronic inflammatory diseases, such as periodontitis. Currently, the mechanisms related to the effects of CR are not yet fully understood. In the present study, we aimed to evaluate the effects of caloric restriction on alveolar bone loss (ABL) in Wistar rats with experimental periodontitis. Main methodsThe impact of CR on biometric data, clinical periodontal parameters, serum biomarkers and biochemical parameters were also investigated. The experimental protocol lasted 24 weeks. The CR rats were fed for 12 weeks with 70% of the standard food compared to the animals with ad libitum diet. Experimental periodontitis was induced in Wistar rats during 15 days before the end of the experiment. The animals were divided into four experimental groups (n = 12 animals/group), according to the presence or absence of caloric restriction and ligature-induced periodontitis. Hemimandibles were used to assess ABL. Key findingsThe groups with experimental periodontitis induction showed a significant decrease on alveolar bone loss in animals submitted to caloric restriction, in addition to attenuating gingival inflammation, demonstrated by the significant difference in gingival index. Biochemical and biometric data showed a significant reduction in the glycemic profile, body weight, adiposity index and abdominal circumference after caloric restriction. Caloric restriction did not significantly alter bone tissue biomarkers. SignificanceAccording to the findings, caloric restriction reduced alveolar bone loss, glycemic profile and biometric parameters in rats with experimental periodontitis.

Change in Visceral Adiposity with a 12-Month Behavioral Weight Loss Intervention with Varying Doses of Physical Activity: The Heart Health Study

Visceral adipose tissue (VAT) is considered to have biochemical characteristics that influence several pathophysiological processes of the body and high levels are associated with increased risk for metabolic syndrome, cardiovascular disease, and certain cancers. There is data to suggest that supervised aerobic exercise may reduce VAT in the absence of caloric restriction. PURPOSE: To examine whether VAT is reduced within the context of a comprehensive weight management program, varied by prescribed levels of home-based moderate-to-vigorous physical activity (MVPA) in adults who were overweight or obese across 12 months. METHODS: Data were examined from sedentary adults (N=309; BMI: 32.3±3.8 kg/m2; age=45.1±7.9 years) enrolled in a behavioral program and randomized to a reduced calorie diet (DIET, N=107), diet plus a moderate dose of MVPA (MOD-EX, N=101), or diet plus a high dose of MVPA (HIGH-EX, N=101). All groups received weekly intervention sessions in months 1-6 followed by 2 group and 2 telephone contacts per month in months 7-12, and were prescribed a diet to reduce energy intake (1200-1800 kcal/day). MOD-EX was prescribed unsupervised MVPA that progressed to 150 min/wk, whereas HIGH-EX was progressed to 250 min/wk. Body composition and VAT were measured by DXA (GE Lunar iDXA, Corescan) along with weight at 0, 6 and 12 months. RESULTS: Weight significantly decreased in all groups at 6 months (DIET: -9.0±5.9 kg, MOD-EX: -10.2±6.4 kg, HIGH-EX: -9.4±5.3 kg; p<0.001) and 12 months (DIET: -10.0±8.3 kg, MOD-EX: -11.1±8.1 kg, HIGH-EX: -9.7±6.9 kg; p<0.001), with no significant difference between groups. A similar pattern was observed for percent body fat (Baseline: 43.3±5.5%, 6-month: 38.3±7.0%, 12-month: 37.7±7.6%; p<0.001) with no difference between groups. VAT decreased across time (Baseline: 1518±907cm3, 6-month: 1018±617cm3, 12-month: 971±648cm3; p<0.001) with no difference between groups. CONCLUSIONS: The interventions were successful at reducing body weight and improving body composition in adults with obesity. The lack of additional weight loss, reductions in body compositon and VAT with participation in MVPA at two different doses may suggest that there is a compensatory response in factors influencing energy balance that warrant further investigation. Supported by: NIH (R01 HL103646)

Physiological and Transcriptomic Analysis of a Chronologically Long-Lived Saccharomyces cerevisiae Strain Obtained by Evolutionary Engineering.

High-throughput aging studies with yeast as a model organism involve transposon-mutagenesis and yeast knockout collection, which have been pivotal strategies for understanding the complex cellular aging process. In this study, a chronologically long-lived Saccharomyces cerevisiae mutant was successfully obtained by using another high-throughput approach, evolutionary engineering, based on systematic selection in successive batch cultures under gradually increasing levels of caloric restriction. Detailed comparative physiological and transcriptomic analyses of the chronologically long-lived mutant and the reference strain revealed enhanced levels of respiratory metabolism, upregulation of genes related to carbohydrate metabolic processes, glycogen-trehalose pathways, stress response, and repression of protein synthesis-related genes in the long-lived mutant SRM11, already in the absence of caloric restriction. Interestingly, SRM11 had also significantly higher resistance to copper stress, and higher resistance to silver, ethanol, and 2-phenylethanol stresses than the reference strain. It also had lower ethanol production levels and an enhanced ethanol catabolism. To conclude, evolutionary engineering is another powerful high-throughput method for aging research, in addition to its widespread use in industrial strain development. Additionally, the interesting results revealed by this study about the potential relationship between longevity and various cellular properties are yet to be investigated further at molecular level.

Effect of Exercise Training on Metabolic Homeostasis and Some Hemodynamics (Some Hepatic and Cardiovascular Functions) in Experimentally Induced Obesity

Background: Obesity is associated with many chronic disorders such as type-2 diabetes mellitus, essential hypertension and non-alcoholic fatty liver disease (NAFLD). High fat diet (HFD) induced obesity in rats is associated with altered adipocytes release of several adipocytokines. Physical exercise has also been shown to have positive effects in the prevention and attenuation of many of the obesity-related disorders, however; the mechanisms have not been fully elucidated. Objective: The present study was designed to examine the effect of moderate intensity exercise training on existing cardio metabolic and hepatic complications linked to obesity including dyslipidemia, insulin resistance, hypertension and NAFLD. Materials and methods: Thirty healthy adult male albino rats of initial body weight 151-190 gm were included. Rats were randomly and equally divided into 3 groups: group (1): normal diet fed group, group (II): HFD induced obesity group in which obesity was induced by HFD for 12 weeks and group (III): HFD induced obesity group fed on high fat diet for 12 weeks then followed by moderate intensity swimming exercise training for 8 weeks. Rats were examined for the body weight, length, abdominal circumference (AC) and body mass index (BMI), Systolic, diastolic & mean arterial blood pressures, heart rate, serum glucose, insulin & HOMA-IR, serum total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) & atherogenic index (AI), serum adiponectin, leptin, irisin, , tumor necrosis factor alpha (TNF- α), Interleukin-6 (IL-6) malondialdehyde (MDA), superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline Phosphatase (ALP), lactate dehydrogenase (LDH) and albumin. Histopathological examination for hepatic tissue was also evaluated. Results: The present study revealed that HFD significantly increased final body weight, BMI, AC, Systolic, diastolic & mean arterial blood pressures, heart rate, serum levels of glucose, insulin, TC, TG, LDL, VLDL, ALT, AST, ALP, LDH, TNF- α, IL-6, MDA and leptin levels, in addition to HOMA-IR and atherogenic index in HFD-induced obesity group. However, there were significant decreases in serum levels of HDL, SOD, albumin, adiponectin and irisin levels in the same group. Histopathological changes in hepatic tissue that indicate the development of NASH were also observed in HFD-induced obesity group. On the other hand, chronic moderate intensity swimming exercise training significantly reversed all these manifestations even in the absence of caloric restriction. Conclusion: moderate exercise training seems to be an effective strategy to reverse almost all risk factors of cardiovascular diseases and NAFLD associated with metabolic syndrome.

Effects of Dairy Products Consumption on Body Weight and Body Composition Among Adults: An Updated Meta-Analysis of 37 Randomized Control Trials.

Effects of dairy consumption on body weight and body composition have been inconsistently observed in randomized control trials (RCTs). Our meta-analysis aims to systematically evaluate the effects of dairy consumption on body weight and body composition among the adults. We conducted a comprehensive search of the Cochrane Library, PubMed, and Embase databases of the relevant studies from 1966 to Mar 2017 regarding dairy consumption on body weight and body composition including body fat, lean mass, and waist circumference (WC). The summary results are pooled by using a random-effects meta-analysis. Thirty-seven RCTs with 184802 participants are included in this meta-analysis. High dairy intervention increased body weight (0.01, 95% CI: -0.25, 0.26, I2 = 78.3%) and lean mass (0.37, 95% CI: 0.11, 0.62, I2 = 83.4%); decreased body fat (-0.23, 95% CI: -0.48, 0.02, I2 = 78.2%) and WC (-1.37, 95% CI: -2.28, -0.46, I2 = 98.9%) overall. In the subgroup analysis, we found that consumption of dairy products increases body weight (0.36, 95% CI: 0.01, 0.70, I2 = 83.1%) among participants without energy restriction. Dairy consumption decreases body weight (-0.64, 95% CI: -1.05, -0.24, I2 = 60.2%), body fat (-0.56, 95%CI: -0.95, -0.17, I2 = 66.6%), and waist circumference (-2.18, 95%CI: -4.30, -0.06, I2 = 99.0%) among the adults with energy restriction. This meta-analysis suggests a beneficial effect of energy-restricted dairy consumption on body weight and body composition. However, high dairy consumption in the absence of caloric restriction may increase body weight.

Leptin is a dose-dependent marker of caloric restriction in adipose tissues located in different parts of the mouse body

We investigated leptin expression in four fat tissues located in different body parts of male mice. In the absence of caloric restriction (CR), the highest relative levels of leptin mRNA were detected in epididymal fat (EF). Lateral abdominal fat (LAF) and subcutaneous fat (SF) had intermediate leptin expression levels, while the lowest leptin mRNA content was revealed in brown adipose tissue (BAT). We also investigated differential regulation of leptin expression in these adipose tissues following diets that were based on various levels of CR for 10 weeks. The largest reduction of leptin mRNA levels by CR was observed in adipose tissue where maximal leptin mRNA expression was detected in the absence of CR. Leptin protein expression was also decreased by CR as revealed by immunohistochemistry. The changes in leptin mRNA and protein expression positively correlated with adipocyte size that was also diminished with the increase in the strength of CR.

Abstract P219: Dairy Consumption and Body Mass Index: Mendelian Randomization Analysis of 184,802 Participants and Systematic Review of 37 Randomized Controlled Trials

Objective: Using the Mendelian randomization (MR) approach and meta-analysis of selected randomized controlled trials (RCTs), we aimed to assess whether dairy intake was causally related to BMI. Methods: We used a genetic polymorphism in MCM6 ( LCT -13910 C/T, rs4988235), located upstream of the lactase gene ( LCT), as an instrumental variable (IV) for dairy intake in a MR design. The causal effect of dairy intake on BMI was quantified by IV estimators among 184,802 participants from 25 studies. We further conducted a new meta-analysis of RCTs on the effect of dairy consumption on changes in body composition among 3,007 participants in 37 RCTs. Results: Higher dairy intake was associated with higher BMI (multivariable-adjusted β = 0.03 kg/m 2 per serving/day; 95% CI, 0.00, 0.06; p=0.04), while the LCT -13910 C/T CT+TT genotype was significantly associated with higher dairy intake (β = 0.20 serving/day; 95% CI, 0.14, 0.25; p=3.15х10 -12 ) and higher BMI (β = 0.12 kg/m 2 ; 95% CI, 0.06, 0.17; p=2.11х10 -5 ). The IV analysis showed that higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m 2 per serving/day; 95% CI, 0.27, 0.92; p=3.0х10 -4 ). In addition, our systematic review of 37 RCTs indicated that higher dairy intervention significantly increased body weight (0.36 kg, 95% CI: 0.01, 0.70) and marginally increased lean mass (0.14 kg, 95% CI: -0.06, 0.33) in trials without energy restriction. Conclusions: The present study provides evidence to support a causal effect of higher dairy intake in the absence of caloric restriction on increased BMI.

Vitamin D supplementation and body weight status: a systematic review and meta‐analysis of randomized controlled trials

Vitamin D is anticipated to have many extra-skeletal health benefits. We questioned whether supplementation with the vitamin influenced body weight and composition. A systematic review and meta-analysis was conducted on high-quality, randomized controlled trials (RCTs) that had supplemented vitamin D without imposing any caloric restriction. Eighteen trials reporting either body weight, body mass index (BMI), fat mass (FM), percentage fat mass (%FM) or lean body mass (LBM) met our criteria. Twelve studies provided the required data for the meta-analysis. Vitamin D supplementation did not influence the standardized mean difference (SMD) for body weight, FM, %FM or LBM. A small but non-significant decrease in BMI (SMD = -0.097, 95% confidence interval: [-0.210, 0.016], P = 0.092) was observed. Meta-regression confirmed that neither the absolute vitamin D status achieved nor its change from baseline influenced the SMD of any obesity measure. However, increasing age of the subjects predicted a shift in the SMD for FM towards the placebo treatment, whereas a greater percentage of women in these studies favoured a decrease in FM following vitamin D. Vitamin D supplementation did not decrease measures of adiposity in the absence of caloric restriction. A potential confounding by age and gender was encountered.

Effects of a leucine and pyridoxine-containing nutraceutical on body weight and composition in obese subjects

BackgroundWe recently demonstrated leucine to modulate energy partitioning between adipose tissue and muscle. Further, leucine exhibits a synergy with B6, resulting in reduced adipocyte lipid storage coupled with increased muscle fat oxidation. Accordingly, a nutraceutical (NuShape™) containing 2.25 g leucine and 30 mg B6 increased fat oxidation by >30 g/day in a 28-day randomized controlled trial. The present study evaluated the long-term efficacy of this combination in modulating body weight and composition.MethodsTwo 24-week, placebo-controlled, randomized trials, one with weight maintenance (n = 20) and one hypocaloric (−500 kcal/day; n = 24), were conducted using the nutraceutical Nushape in obese subjects.ResultsThe supplement resulted in fat loss in the maintenance study (−1.12 ± 0.36 and −1.82 ± 0.70 kg at 12 and 24 weeks, P < 0.01 versus placebo) while no change was found in the placebo group. In the hypocaloric study, the supplement group lost up to twice as much weight (6.18 ± 1.02 versus 3.40 ± 0.81 kg at 12 weeks and 8.15 ± 1.33 versus 5.25 ± 1.13 kg at 24 weeks, P < 0.01) and fat (4.96 ± 0.61 versus 2.31 ± 0.53 kg at 12 weeks and 7.00 ± 0.95 versus 4.22 ± 0.74 kg at 24 weeks, P < 0.01) than the placebo group.ConclusionThis nutraceutical combination results in significant fat loss in the absence of caloric restriction and markedly enhances weight and fat loss by 50%–80% over a 24-week period.

Hunger in the Absence of Caloric Restriction Improves Cognition and Attenuates Alzheimer's Disease Pathology in a Mouse Model

It has been shown that caloric restriction (CR) delays aging and possibly delays the development of Alzheimer's disease (AD). We conjecture that the mechanism may involve interoceptive cues, rather than reduced energy intake per se. We determined that hunger alone, induced by a ghrelin agonist, reduces AD pathology and improves cognition in the APP-SwDI mouse model of AD. Long-term treatment with a ghrelin agonist was sufficient to improve the performance in the water maze. The treatment also reduced levels of amyloid beta (Aβ) and inflammation (microglial activation) at 6 months of age compared to the control group, similar to the effect of CR. Thus, a hunger-inducing drug attenuates AD pathology, in the absence of CR, and the neuroendocrine aspects of hunger also prevent age-related cognitive decline.

Effects of a leucine and pyridoxine‐containing nutraceutical on body weight and composition in obese adults

We recently demonstrated leucine to modulate energy partitioning between adipose tissue and muscle. Further, leucine exhibits a synergy with B6, resulting in reduced adipocyte lipid storage coupled with increased muscle fat oxidation. A nutraceutical (NuShape) containing 2.25 g leucine and 30 mg B6 increased fat oxidation by &gt;;30 g/d in a 28‐day RCT. To evaluate the efficacy of this combination in modulating body weight and composition, we conducted two 24‐week placebo‐controlled RCTs, one with weight maintenance (n=20) and one hypocaloric (−500 kcal/d; n=24). The supplement resulted in fat loss in the maintenance study (−1.12±0.36 and −1.82±0.70 kg at 12 and 24 weeks, p&lt;0.01 vs placebo) while no change was found in the placebo‐group. In the hypocaloric study, the supplement group lost up to twice as much weight (6.18±1.02 vs. 3.40±0.81 kg at 12 weeks and 8.15±1.33 vs. 5.25±1.13 kg at 24 weeks, p&lt;0.01) and fat (4.96±0.61 vs. 2.31±0.53 kg at 12 weeks and 7.00±0.95 vs. 4.22±0.74 kg at 24 weeks, p&lt;0.01) than placebo. Thus, this nutraceutical combination results in significant fat loss in the absence of caloric restriction and markedly enhances weight and fat loss by 50–80% over a 24‐week period.

Vitamin D supplementation increases true fractional calcium absorption in the absence of caloric restriction

Caloric restriction is associated with a decrease in true fractional calcium absorption (TFCA). We examined whether vitamin D supplementation would attenuate the decrease in TFCA associated with weight loss (WL). Seventy‐seven women (58 ± 5.9 years of age; BMI of 30.2 ± 3.6 kg/m2; serum 25‐hydroxyvitamin D [25OHD] = 24.8 ± 5.7 ng/mL) were randomized into 4 groups (n=18–20/group) to receive either vitamin D supplementation (D) or placebo (Pl) and undergo WL or maintain their body weight (WM) over 6 weeks. The women received either 2500 IU/d [2100 IU D3 plus 400 IU from multivitamin (MV)] or 400 IU/d [Placebo plus 400 IU from MV] of vitamin D3 with 1.2 g Ca/d in all groups. Subjects in the WL group lost 3.8 ± 1.2% body weight with no differences between the D or Pl groups. Vitamin D did not influence calcitriol (1,25OH2D) but increased 25OHD. The 25OHD rise was greater during WL (WL‐D, +8 ± 6 ng/mL) vs. WM‐D (+3 ± 4 ng/m) (p &lt; 0.01). WL decreased TFCA (p&lt;0.01). D treatment suppressed PTH and increased TFCA (p&lt;0.02). The TFCA change from baseline was greater (p &lt; 0.01) in WM‐D (+0.037 ± 0.052) than WL‐D (−0.006 ± 0.036). TFCA change in the WL‐D group did not differ significantly from the WL‐Pl group (−0.026 ± 0.039). Since the rise in 25OHD in the WL‐D was more than double the WM‐D group and there was no rise in 1,25OH2D, other mechanisms are likely also contributing to the regulation of TFCA during caloric restriction. Supported by NIH‐AG12161.

The effects of hunger in the absence of caloric restriction in a mouse model of Alzheimer's disease

The effects of hunger in the absence of caloric restriction in a mouse model of Alzheimer's disease

Effect of Ketogenic Diet on Survival of Magnocellular Neurons Following Infundibular Nerve Crush Injury

Our experimental objectives were to first determine the effect of two ketogenic diet (KD) formulations on neuroendocrine function and determine the extent to which these ketogenic diets increase plasma ketone levels in rats. Second, we sought to determine the effect of KD and its specific metabolites on alleviation of traumatic brain injury (TBI) ‐induced diabetes insipidus (DI) and the survival of compromised supraoptic magnocellular neurons that are selectively vulnerable to TBI insult.Methods utilized included immunocytochemical and metabolic analysis, stereometric assessment of neuronal survival, analysis of plasma ß‐hydroxybutyrate and acetoacetate levels, and infundibular nerve crush.Our results demonstrate that after a 4 week administration of 18% protein KD, plasma ketone levels of β‐hydroxybutyrate and acetoacetate were significantly increased over control diet values in the absence of caloric restriction. Plasma ketone body levels were also significantly increased with 8% protein KD although there was marked caloric restriction associated with this formulation. Interestingly, the 18% protein KD had substantially higher ketone body levels than the 8% protein KD. However, despite increased ketone body levels, no improvement in survival of magnocellular supraoptic neurons was observed following infundibular nerve crush. Nor was there any dietary effect on alleviation of injury induced DI.

A Cool Way to a Long Life

Caloric dietary restriction prolongs life span in a variety of organisms, and in mammals, the resultant lowering of core body temperature has been offered as one potential explanation. Conti et al . generated transgenic mice that overexpress mitochondrial uncoupling protein 2 in hypocretin-producing neurons within the hypothalamus, which lowers core body temperature by about 0.5ºC. In the absence of caloric restriction, the median life span of these "cool mice" was about 15% greater than that of their wild-type littermates. B. Conti, M. Sanchez-Alavez, R. Winsky-Sommerer, M. C. Morale, J. Lucero, S. Brownell, V. Fabre, S. Huitron-Resendiz, S. Henriksen, E. P. Zorrilla, L. de Lecea, T. Bartfai, Transgenic mice with a reduced core body temperature have an increased life span. Science 314 , 825-828 (2006). [Abstract] [Full Text] C. B. Saper, Life, the universe, and body temperature. Science 314 , 773-774 (2006). [Abstract] [Full Text]

Role of calcium and dairy products in energy partitioning and weight management

Dietary calcium plays a pivotal role in the regulation of energy metabolism because high-calcium diets attenuate adipocyte lipid accretion and weight gain during the overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, which thereby markedly accelerates weight loss. Intracellular Ca(2+) plays a key regulatory role in adipocyte lipid metabolism and triacylglycerol storage; increased intracellular Ca(2+) results in the stimulation of lipogenic gene expression and lipogenesis and the suppression of lipolysis, which results in increased lipid filling and increased adiposity. Moreover, the increased calcitriol produced in response to low-calcium diets stimulates adipocyte Ca(2+) influx and, consequently, promotes adiposity, whereas higher-calcium diets inhibit lipogenesis, inhibit diet-induced obesity in mice, and promote lipolysis, lipid oxidation, and thermogenesis. Notably, dairy sources of calcium markedly attenuate weight and fat gain and accelerate fat loss to a greater degree than do supplemental sources of calcium. This augmented effect of dairy products relative to supplemental calcium is likely due to additional bioactive compounds, including the angiotensin-converting enzyme inhibitors and the rich concentration of branched-chain amino acids in whey, which act synergistically with calcium to attenuate adiposity. These concepts are confirmed by epidemiologic data and recent clinical trials, which indicate that diets that include > or =3 daily servings of dairy products result in significant reductions in adipose tissue mass in obese humans in the absence of caloric restriction and markedly accelerate weight and body fat loss secondary to caloric restriction compared with diets low in dairy products. These data indicate an important role for dairy products in both the prevention and treatment of obesity.

Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease

Inflammation and the recruitment of monocytes into the artery wall are thought to be important aspects in the initiation and progression of atherosclerosis. The present study was designed to examine the effects of a rigorous diet and exercise intervention on plasma lipids and inflammatory and circulating adhesion molecules. Twenty postmenopausal women at risk for coronary artery disease (CAD) were placed on a high-fiber, low-fat diet, where food was provided ad libitum and daily aerobic exercise, primarily walking, was performed. In each subject, pre- and postintervention fasting blood was drawn for serum lipid, insulin, glucose, C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and both soluble (s) intracellular and vascular adhesion molecule (sICAM-1 and sVCAM-1) were measured. After 2 weeks, significant reductions in body mass index (BMI) ( P < .001), glucose ( P < .05), insulin ( P < .01), all serum lipids, and total cholesterol (total-C):high-density lipoprotein-cholesterol (HDL-C) ( P < .01). Reductions in homeostasis model assessment for insulin resistance (HOMA-IR) ( P < .01), CRP ( P < .01), SAA ( P < .01) and sICAM-1 ( P < .05) were noted, as well as an increase in the quantitative insulin sensitivity check index ( P < .05). Reductions were also noted in 5 women not using hormone replacement therapy (HRT). No significant reductions were found in IL-6 or sVCAM-1 in response to the intervention. Overall, this intervention resulted in improved metabolic and lipid profiles, reduced inflammatory, and cell adhesion molecules in postmenopausal women in the absence of caloric restriction. The rapid improvements may reduce the risk of acute myocardial infarction (MI), and if sustained, these changes may mitigate the risk for atherosclerosis progression and its clinical consequences.

Role of dietary calcium and dairy products in modulating adiposity.

Dietary calcium plays a pivotal role in the regulation of energy metabolism. High-calcium diets attenuate adipocyte lipid accretion and weight gain during overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Our studies of the agouti gene demonstrate a key role for intracellular Ca2+ in regulating adipocyte lipid metabolism and TG storage. Increased intracellular Ca2+ resulting in stimulation of lipogenic gene expression, and lipogenesis and suppression of lipolysis resulting in adipocyte lipid filling and increased adiposity. Moreover, we recently demonstrated that the increased calcitriol produced in response to low-calcium diets stimulates adipocyte Ca2+ influx and, consequently, promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for obesity intervention. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low-calcium diets with accelerated weight gain and fat accretion, whereas high-calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis, and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low-calcium diets impede body fat loss, whereas high-calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. Dairy sources of calcium exert markedly greater effects in attenuating weight and fat gain and accelerating fat loss. This augmented effect of dairy products is likely due to additional bioactive compounds in dairy that act synergistically with calcium to attenuate adiposity. These concepts are confirmed by both epidemiological and clinical data, which demonstrate that increasing dietary calcium results in significant reductions in adipose tissue mass in obese humans in the absence of caloric restriction and markedly accelerates the weight and body fat loss secondary to caloric restriction, whereas dairy products exert significantly greater effects. These data indicate an important role for dairy products in both the prevention and treatment of obesity.