Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults

Introduction: Inter-individual response to dietary interventions remains a major challenge to successful weight loss among older adults. This study applied metabolomics technology to identify small molecule signatures associated with loss of fat mass and overall weight in a cohort of older adults on a nutritionally complete, high protein diet. Methods: 102 unique metabolites were measured using LC-MS for 38 adults aged 65-80 years randomized to dietary intervention and 36 controls. Metabolite values were analyzed in both baseline plasma samples and samples collected following the six-month dietary intervention to consider both metabolites that could predict response to diet and those that changed in response to diet or weight loss. Results: Eight metabolites changed over intervention at a nominally-significant level: D-pantothenic acid, L-methionine, nicotinate, aniline, melatonin, deoxycarnitine, 6-deoxy-L-galactose, and 10-hydroxydecanoate. Within the intervention group, there was broad variation in achieved weight-loss and DXA-defined changes in total fat and visceral adipose tissue (VAT) mass. Change in VAT mass was significantly associated with baseline abundance of α-aminoadipate (p = 0.0007) and an additional mass spectrometry peak that may represent D-fructose, myo-inositol, mannose, α-D-glucose, allose, D-galactose, D-tagatose, or L-sorbose (p = 0.0001). Discussion: This hypothesis-generating study reflects the potential of metabolomic biomarkers for the development of personalized dietary interventions.

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Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults

Nutrients ◽

10.3390/nu12103188 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3188

Author(s):

Ellen E. Quillen ◽

Daniel P. Beavers ◽

Anderson O’Brien Cox ◽

Cristina M. Furdui ◽

Jingyun Lee ◽

...

Keyword(s):

Mass Spectrometry ◽

Older Adults ◽

Weight Loss ◽

Dietary Intervention ◽

Intervention Group ◽

Pantothenic Acid ◽

High Protein Diet ◽

Individual Response ◽

Dietary Interventions ◽

Intentional Weight Loss

Inter-individual response to dietary interventions remains a major challenge to successful weight loss among older adults. This study applied metabolomics technology to identify small molecule signatures associated with a loss of fat mass and overall weight in a cohort of older adults on a nutritionally complete, high-protein diet. A total of 102 unique metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) for 38 adults aged 65–80 years randomized to dietary intervention and 36 controls. Metabolite values were analyzed in both baseline plasma samples and samples collected following the six-month dietary intervention to consider both metabolites that could predict the response to diet and those that changed in response to diet or weight loss.Eight metabolites changed over the intervention at a nominally significant level: D-pantothenic acid, L-methionine, nicotinate, aniline, melatonin, deoxycarnitine, 6-deoxy-L-galactose, and 10-hydroxydecanoate. Within the intervention group, there was broad variation in the achieved weight-loss and dual-energy x-ray absorptiometry (DXA)-defined changes in total fat and visceral adipose tissue (VAT) mass. Change in the VAT mass was significantly associated with the baseline abundance of α-aminoadipate (p = 0.0007) and an additional mass spectrometry peak that may represent D-fructose, myo-inositol, mannose, α-D-glucose, allose, D-galactose, D-tagatose, or L-sorbose (p = 0.0001). This hypothesis-generating study reflects the potential of metabolomic biomarkers for the development of personalized dietary interventions.

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A 12-week multi-component dietary intervention improves markers of non-alcoholic fatty liver disease in Irish patients in tertiary care

Proceedings of The Nutrition Society ◽

10.1017/s002966512000453x ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Deirdre Ní Fhloinn ◽

Ciara Wright ◽

Sara Naimimohasses ◽

Stephen Finn ◽

Suzanne Norris ◽

...

Keyword(s):

Weight Loss ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Dietary Intervention ◽

Tertiary Care ◽

Intervention Group ◽

Post Intervention ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is a significant public health concern closely linked to obesity, affecting an estimated 25% of adults in Europe. Understudied in Ireland, the aim of this research was to examine the effects of a 12-week multi-component dietary intervention on weight loss and markers of liver injury in Irish NAFLD patients in tertiary care. Biopsy confirmed NAFLD patients (n = 27) were recruited from St James’ Hospital in Dublin, Ireland. Consenting participants underwent a 12-week moderate-intensity intervention incorporating weekly group nutritional education, behavioural change and group support, as well as individualised advice and weigh-ins from a trained nutritionist. Control group participants were given routine clinical care. All participants were clinically reviewed before, immediately after, and 3 months post intervention. Individuals (n = 12) with histological evidence of steatohepatitis underwent a repeat liver biopsy on completion of the intervention. Detailed dietary assessment was performed using both a 4-day diet diary (4DDD) and a novel, recently validated, short food frequency questionnaire (SFFQ) designed specifically to assess habitual intakes of food items related to NAFLD. Nutrient intakes were analysed using myFood24TM dietary analysis software, and the Mediterranean diet quality score (MDQS) was used to assess the overall change in dietary patterns. Of the 15 participants who completed the intervention, 80% (n = 12) achieved a weight loss exceeding 5%, with 47% (n = 7) achieving > 7%. There were significant improvements from baseline to week 12 in the intervention group for the majority of clinical parameters including HbA1c (p = 0.0054), liver enzymes (ALT, p = 0.0108; GGT, p = 0.0001) and transient elastography (kPA, p = 0.0308; CAP, p = 0.0081). However, these results failed to maintain significance when analysed compared to controls. The overall dietary pattern was significantly improved after 12 weeks as assessed by the MDQS (p = 0.03), with no apparent compromise in micronutrient intake despite the energy reduction. Reductions in energy, saturated fat, carbohydrate and sugar intakes at 12 weeks, were maintained at three months follow up. Analysis of pre- and post-intervention liver biopsies in the intervention group demonstrated a clinically significant improvement in NAS score (p = 0.0273), attributable to reductions in hepatic steatosis (p = 0.0078). A significant correlation was observed between improvement in liver histology and change in sugar intake (r = 0.7534, p = 0.0093). Although results were somewhat limited by small sample size, nutritional education achieved beneficial dietary changes that persisted after the intervention ceased. Notably, achieving reductions in sugar intakes may be particularly beneficial in reducing the severity of hepatic steatosis in Irish adults with NAFLD.

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Abstract 3610: Comparative Effects of 3 Popular Diets on Lipids, Endothelial Function and Biomarkers of Atherothrombosis in the Absence of Weight Loss

Circulation ◽

10.1161/circ.116.suppl_16.ii_819 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Michael Miller ◽

Valerie Beach ◽

Charles Mangano ◽

Jeffrey Rhyne ◽

Christina Dobmeier ◽

...

Keyword(s):

Weight Loss ◽

Endothelial Function ◽

Cardiovascular Health ◽

Dietary Intervention ◽

Saturated Fat ◽

Inverse Correlation ◽

Monounsaturated Fat ◽

The South ◽

Atkins Diet ◽

Total Fat

Background : While the effect of popular diets on weight loss has been extensively studied, less is known in the absence of weight loss. We hypothesized that a diet high in total and saturated fat would be associated with adverse effects on LDL-C, endothelial function and biomarkers of atherothrombosis compared to lower fat diets. Methods : We tested 3 popular diets, including Atkins (50% fat), South Beach (30% fat) and Ornish (10% fat) in a randomized and counterbalanced, crossover study. Subjects completed each of the three 4-week dietary intervention phases followed by a 4-week washout period. They were weighed weekly and caloric adjustments made if weight change exceeded 1 kg. At the completion of each dietary phase, 3-day food records were analyzed, fasting blood was sampled and brachial artery reactivity testing (BART) performed. Results : Eighteen of 26 adults (mean age: 30.6 ± 9.6 yrs, 50% female) completed all 3 dietary phases. There were no changes in weight at the conclusion of each phase. However, non-significant increases in LDL-C occurred during the Atkins phase (pre: 96.5, post: 112.9 mg/dL; P=0.12 ), whereas LDL-C was reduced during the Ornish (pre: 110.1, post: 84.6 mg/dL; P=0.006 ) and South Beach phases (pre: 101.7, post: 91.5 mg/dL; P=0.01 ). BART testing revealed a significant inverse correlation between flow-mediated vasodilation and intake of total fat (r 2 =−0.29; P=0.03 ), saturated fat (r 2 =−0.31; P=0.02 ) and monounsaturated fat (r 2 =−0.35; P=0.01 ). Microarray analysis demonstrated increased expression of several leukocyte biomarkers including, ICAM2 (37%; P=0.002 ), SELL (26%; P=0.007 ) and SOD1 (42%; P=0.04 ) at the completion of the Atkins diet compared to baseline. In contrast, expression of atherothrombotic biomarkers was not increased after the South Beach or Ornish phase. Conclusions: In the absence of weight loss, the high fat Atkins diet is associated with increased LDL-C, reduced endothelial vasoreactivity and increased expression of biomarkers of atherothrombosis. As such, these data suggest that isocaloric conversion to the Atkins diet may negatively impact cardiovascular health as compared to the South Beach or Ornish Diet.

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Effect of Intentional Weight Loss on Mortality Biomarkers in Older Adults With Obesity

The Journals of Gerontology Series A ◽

10.1093/gerona/gly192 ◽

2018 ◽

Vol 74 (8) ◽

pp. 1303-1309 ◽

Cited By ~ 2

Author(s):

Lauren N Shaver ◽

Daniel P Beavers ◽

Jessica Kiel ◽

Stephen B Kritchevsky ◽

Kristen M Beavers

Keyword(s):

Older Adults ◽

Weight Loss ◽

Cystatin C ◽

Healthy Aging ◽

Fasting Blood Glucose ◽

Observational Research ◽

Digit Symbol Substitution Test ◽

Intentional Weight Loss ◽

Meta Analyses ◽

Hai Score

Abstract Background Observational research has identified several mortality biomarkers; however, their responsiveness to change is unknown. We tested whether the Healthy Aging Index (HAI) and other mortality biomarkers were responsive to intentional weight loss (WL), which is associated with lower mortality risk in recent meta-analyses. Methods Older adults (70.3 ± 3.7 years) with obesity were randomized into a 6-month WL (n = 47) or weight stability (WS: ±5% baseline weight; n = 48) program. Baseline and 6-month HAI score (0–10) was calculated from component sum (each 0–2: systolic blood pressure, forced vital capacity [FVC], creatinine, fasting blood glucose [FBG], Montreal Cognitive Assessment), and gait speed, grip strength, Digit Symbol Substitution Test, FEV1, Interleukin-6, C-Reactive Protein, and Cystatin-C were assessed at baseline and 6 months. Results Mean baseline HAI was 3.2 ± 1.6. By 6 months, WL participants lost 8.87 (95% CI: −10.40, −7.34) kg, whereas WS participants remained weight stable. WL group reduced HAI score (WL: −0.75 [95% CI: −1.11, −0.39] vs WS: −0.22 [95% CI: −0.60, 0.15]; p = .04), and components changing the most were FBG (WL: −3.89 [95% CI: −7.78, 0.00] mg/dL vs WS: 1.45 [95% CI: −2.61, 5.50] mg/dL; p = .047) and FVC (WL: 0.11 [95% CI: −0.01, 0.23] L vs WS: −0.05 [95% CI: −0.17, 0.08] L; p = .06). Among other biomarkers, only Cystatin-C significantly changed (WL: −2.53 [95% CI: −4.38, −0.68] ng/mL vs WS: 0.07 [95% CI: −1.85, 1.98] ng/mL; p = .04). Combining treatment groups, 1 kg WL was associated with a 0.07 (95% CI: 0.03, 0.12) HAI reduction (p < .01). Conclusion Intentional WL via caloric restriction reduced HAI score by 0.53 points, largely attributable to metabolic and pulmonary improvements.

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Changes in Cardiometabolic Risk Among Obese Older Adults After a 12-Month Exercise and Diet Intervention

Current Developments in Nutrition ◽

10.1093/cdn/nzaa063_010 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1612-1612

Author(s):

Anna Bragg ◽

Kristi Crowe-White ◽

Amy Ellis ◽

Julie Locher ◽

Jamy Ard ◽

...

Keyword(s):

Older Adults ◽

Weight Loss ◽

Cardiometabolic Risk ◽

Weight Maintenance ◽

Exercise Group ◽

Group Differences ◽

Intentional Weight Loss ◽

Time Interaction ◽

Weight Loss Group ◽

Syndrome Classification

Abstract Objectives Obesity imposes risk to cardiometabolic health; however, intentional weight loss in obese older adults remains controversial. Using data from the CROSSROADS Study (clinicaltrials.gov #NCT00955903), this ancillary study investigated effects of exercise with and without intentional weight loss on changes in cardiometabolic risk assessed by four risk-scoring tools. Methods Participants (n = 134, 39% male, 23% African American, 70.2 ± 4.7 y) were randomized to exercise (n = 48), exercise + nutrient-dense weight maintenance diet (n = 44), or exercise + nutrient-dense caloric restriction of 500 kcals/day (n = 42). The following risk scores were calculated using baseline and 12-month data: Framingham risk assessment, Cardiometabolic Disease Staging (CMDS), metabolic syndrome classification by the International Diabetes Federation (IDF), and metabolic syndrome classification by the National Cholesterol Education Program's Adult Treatment Panel (ATP III). Generalized Estimating Equations were employed to determine differences between groups with ethnicity, sex, and age as covariates. Results Group-time interaction was not significant in application of IDF or ATPIII. Group-time interaction was significant for Framingham and CMDS (P = 0.005 and 0.041, respectively). Upon post-hoc analysis, significant within-group improvements in Framingham scores were observed for exercise + weight maintenance (P < 0.001, r = −1.682) and exercise + weight loss (P = 0.020, r = −0.881). In analysis of between-group differences in Framingham scores, a significant decrease was observed in the exercise + weight maintenance group (P = 0.001, r = −1.723) compared to the exercise group. For CMDS, the exercise + weight loss group had significant within-group improvements (P = 0.023, r = - 0.102). For between-group differences in CMDS, the exercise + weight loss group showed significant risk score reduction (P = 0.012, r = −0.142) compared to the exercise group. Conclusions Risk assessment by Framingham and CMDS showed greater sensitivity to change in cardiometabolic risk factors. Results suggest obese older adults can lower cardiometabolic risk by engaging in exercise + weight maintenance or exercise + weight loss by moderate caloric restriction. Funding Sources R01AG033094 NIA, K07AG043588 NIA, P30DK056336 NIDDK.

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Obesity, intentional weight loss and physical disability in older adults

Obesity Reviews ◽

10.1111/j.1467-789x.2009.00679.x ◽

2010 ◽

Vol 11 (9) ◽

pp. 671-685 ◽

Cited By ~ 75

Author(s):

W. J. Rejeski ◽

A. P. Marsh ◽

E. Chmelo ◽

J. J. Rejeski

Keyword(s):

Older Adults ◽

Weight Loss ◽

Physical Disability ◽

Intentional Weight Loss

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Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS

Reproduction ◽

10.1530/rep-16-0385 ◽

2017 ◽

Vol 153 (1) ◽

pp. R15-R27 ◽

Cited By ~ 6

Author(s):

Brittany Y Jarrett ◽

Marla E Lujan

Keyword(s):

Weight Loss ◽

Dietary Intervention ◽

Polycystic Ovary ◽

Reproductive Function ◽

Antral Follicle ◽

Reproductive Age ◽

Obese Women ◽

Dietary Interventions ◽

Wide Range ◽

The Impact

Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction affecting women of reproductive age. Obesity and insulin resistance are thought to potentiate disruptions in antral follicle development that result in chronic anovulation, and as such, have become important therapeutic targets of dietary interventions aimed at weight loss. Caloric restriction has been shown to promote sporadic ovulation in obese women with PCOS, but improvements have occurred across a wide range of patients and little has been garnered about the factors that distinguish responders from non-responders. Further, few studies have evaluated the likelihood for modest weight loss to restore normal ovulatory cyclicity in PCOS. Consensus regarding the impact of dietary intervention on ovulation has been limited by variability in the measures used to characterize and report ovulatory status across studies. In response, this review provides an assessment of the evidence surrounding the effectiveness of hypocaloric dietary intervention to normalize ovulatory function in PCOS. The impact of physiological vs methodological factors on the evaluation of ovulatory status is discussed, and recommendations to strengthen future studies in this area are provided. Ultimately, further research is needed to understand the optimal dietary or lifestyle approaches that promote ovulation and sustained improvements in reproductive function in PCOS.

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