Position of the Academy of Nutrition and Dietetics: Medical Nutrition Therapy Behavioral Interventions Provided by Dietitians for Adults With Overweight or Obesity, 2024.

Providing interventions that facilitate improvement of dietary intake and other health behaviors can improve nutrition-related outcomes in adults with overweight or obesity. Medical nutrition therapy (MNT) behavioral interventions require expertise from registered dietitian nutritionists or international equivalents (dietitians), which no other health care provider can provide for adults with obesity. Current evidence supports the role of MNT behavioral interventions for adults with overweight or obesity as an effective treatment option, when appropriate for and desired by the client. This Academy of Nutrition and Dietetics Position Paper describes potential benefits and concerns regarding dietitian-provided MNT behavioral interventions for adults with overweight and obesity and informs dietitians about implications for practice. This Position Paper is supported by a systematic review examining effectiveness of MNT interventions provided by dietitians and by an evidence-based practice guideline. It is the position of the Academy of Nutrition and Dietetics that MNT behavioral interventions for adults (aged 18 years and older) with overweight or obesity should be a treatment option, when appropriate and desired by the client, to improve cardiometabolic, quality of life, and anthropometric outcomes. Dietitians providing MNT recognize the complex contributors to overweight and obesity, and thus individualize interventions, based on a shared decision-making process, and deliver interventions in an inclusive, compassionate, and client-centered manner. Interventions should include collaboration with an interprofessional team when needed. Dietitians strive to increase health equity and reduce health disparities by advocating and providing opportunities for increased access to effective nutrition care services. This position remains in effect until December 31, 2031.

Weight Management Interventions Provided by a Dietitian for Adults with Overweight or Obesity: An Evidence Analysis Center Systematic Review and Meta-Analysis.

BACKGROUND: Obesity is associated with a multitude of comorbidities and considerable health care costs. OBJECTIVE: The objective of this review was to examine the efficacy of weight management interventions provided by a registered dietitian or international equivalent (referred to as "dietitian"). METHODS: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the effect of weight management interventions provided by a dietitian, compared with usual care or no intervention, on several cardiometabolic outcomes and quality of life in adults with overweight or obesity. MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and CINAHL databases were searched for eligible RCTs published between January 2008 and January 2021 in the English language. Meta-analyses were conducted using a random-effects model, publication bias was assessed using funnel plots and Egger's statistics, and heterogeneity was assessed by interpreting I2 values. Efficacy of intervention components, such as telehealth or group contacts, were explored in sub-group analyses. Version 2 of the risk-of-bias tool for RCTs was used to assess risk of bias. The Grading of Recommendations Assessment, Development and Evaluation method was used to determine certainty of evidence. RESULTS: This systematic review included 62 RCTs. Compared with control conditions, weight management interventions provided by a dietitian resulted in improved body mass index (mean difference [MD] -1.5; 95% CI -1.74 to -1.26; moderate evidence certainty); percent weight loss (MD -4.01%; 95% CI -5.26% to -2.75%; high evidence certainty); waist circumference (MD -3.45 cm; 95% CI -4.39 to -2.51 cm; high evidence certainty); blood pressure (MD -3.04 mm Hg; 95% CI -5.10 to -0.98 mm Hg and MD -1.99 mm Hg; 95% CI -3.02 to -0.96 mm Hg for systolic blood pressure and diastolic blood pressure, respectively; moderate and low evidence certainty); and quality of life using the 36-Item Short Form Survey (MD 5.84; 95% CI 2.27 to 9.41 and 2.39; 95% CI 1.55 to 3.23 for physical and mental quality of life, respectively; low and moderate evidence certainty). CONCLUSIONS: For adults with overweight or obesity, weight management interventions provided by a dietitian are efficacious for improving several examined cardiometabolic outcomes and quality of life.

Medical Nutrition Therapy Interventions Provided by Dietitians for Adult Overweight and Obesity Management: An Academy of Nutrition and Dietetics Evidence-Based Practice Guideline.

Overweight and obesity affect most adults living in the United States and are causally linked to several adverse health outcomes. Registered dietitian nutritionists or international equivalents (dietitians) collaborate with each client and other health care professionals to meet client-centered goals, informed by the best available evidence, and translated through a lens of clinical expertise and client circumstances and preferences. Since the last iteration of the Academy of Nutrition and Dietetics guideline on adult weight management in 2014, considerable research has been conducted and circumstances confronting dietitians have evolved. Thus, updated guidance is needed. The objective of this evidence-based practice guideline is to provide recommendations for dietitians who deliver medical nutrition therapy behavioral interventions for adults (18 years and older) with overweight and obesity to improve cardiometabolic outcomes, quality of life, and weight outcomes, when appropriate for and desired by the client. Recommendations in this guideline highlight the importance of considering complex contributors to overweight and obesity and individualizing interventions to client-centered goals based on specific needs and preferences and shared decision making. The described recommendations have the potential to increase access to care and decrease costs through utilization of telehealth and group counseling as effective delivery methods, and to address other barriers to overweight and obesity management interventions. It is essential for dietitians to collaborate with clients and interprofessional health care teams to provide high-quality medical nutrition therapy interventions using the nutrition care process to promote attainment of client-centered outcomes for adults with overweight or obesity.

Adipose Tissue Inflammation Is Not Related to Adipose Insulin Resistance in Humans.

The role of adipose tissue (AT) inflammation in AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression, and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC50). We studied 86 volunteers with normal weight or obesity at baseline and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong positive relationship between IC50 and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC50 and abdominal AT inflammatory markers CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6, and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC50; however, there was no reduction in adipose ATM content, senescent cells, or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.

Senescent cells in human adipose tissue: A cross-sectional study.

OBJECTIVE: Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation. METHODS: Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated ß-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured. RESULTS: There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI: 0.98%-2.3%], p < 0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%, p < 0.01). There was a positive correlation between senescence and fat cell size in abdominal (rs  = 0.44, p < 0.001) and femoral (rs  = 0.35, p = 0.007) AT depots. Abdominal AT tumor necrosis factor alpha (rs  = 0.49, p < 0.01) and interleukin-1ß (rs  = 0.44, p = 0.01) expression was positively correlated with abdominal, but not femoral, AT senescence. CONCLUSIONS: In human subcutaneous AT, there are more senescent cells in femoral than abdominal depots; abdominal AT senescent cells are more associated with inflammatory signals than femoral AT senescent cells.

Adipose tissue macrophage burden, systemic inflammation, and insulin resistance.

Adipose tissue inflammation, as defined by macrophage accumulation, is proposed to cause insulin resistance and systemic inflammation. Because the strength of this relationship for humans is unclear, we tested whether adipose tissue macrophage (ATM) burden is correlated with these health indicators. Using immunohistochemistry, we measured abdominal subcutaneous CD68+ (total ATM), CD14+ (proinflammatory/M1), and CD206+ (anti-inflammatory/M2) ATM in 97 volunteers (BMI 20-38 kg/m2, in addition to body composition, adipocyte size, homeostasis model assessment of insulin resistance, ADIPO-IR, adipose tissue insulin resistance measured by palmitate, plasma lipids, TNF, and IL-6 concentrations. There were several significant univariate correlations between metabolic parameters to IL-6 and ATM per 100 adipocytes, but not ATM per gram tissue; adipocyte size was a confounding variable. We used matching strategies and multivariate regression analyses to investigate the relationships between ATM and inflammatory/metabolic parameters independent of adipocyte size. Matching approaches revealed that the groups discordant for CD206 but concordant for adipocyte size had significantly different fasting insulin and IL-6 concentrations. However, groups discordant for adipocyte size but concordent for ATM differeded in that visceral fat, plasma triglyceride, glucose, and TNF concentrations were greater in those with large adipocytes. Multivariate regression analysis indicated that indexes of insulin resistance and fasting triglycerides were predicted by body composition; the predictive value of ATM per 100 adipocytes or per gram tissue was variable between males and females. We conclude that the relationship between ATM burden and metabolic/inflammatory variables is confounded by adipocyte size/body composition and that ATM do not predict insulin resistance, systemic inflammation, or dyslipidemia. ATM may primarily play a role in tissue remodeling rather than in metabolic pathology.

Preliminary evidence for reduced adipose tissue inflammation in vegetarians compared with omnivores.

BACKGROUND: There are links between obesity and inflammation that may relate activation of pro-inflammatory pathways by dietary factors. Because dietary fat intake of vegetarians is thought to be more beneficial than that of omnivores, we hypothesized that obese vegetarians would have less adipose tissue inflammation and lower intramyocellular ceramide concentrations than equally obese omnivores. METHODS: Eight obese vegetarian (1 male) and 8 obese omnivore volunteers (1 male) completed a Food Frequency Questionnaire, underwent body composition measures, subcutaneous adipose tissue and muscle biopsies. We used immunohistochemistry to measure adipose macrophage (ATM) and senescent cells. Plasma free fatty acid (FFA), adipose FA and muscle ceramide profiles were measured using liquid chromatography/mass spectrometry. Student t tests were used for the comparison of primary outcomes; univariate regression analysis was used to test for associations between dietary patterns and ATMs (secondary analysis). RESULTS: There were no differences in age (38 ± 8 vs. 39 ± 8 years), BMI (32.2 ± 2.6 vs. 33.3 ± 1.9 kg/m2) or percent body fat (44 ± 8 vs. 45 ± 4) between the vegetarians and omnivores. Vegetarians consumed 42% (P = 0.02) less saturated fat and 50% (P = 0.04) less cholesterol than the omnivores. Plasma FFA of vegetarians had lesser proportions of palmitic acid (24 ± 3 vs. 29 ± 4%, P = 0.02) and vegetarians had fewer femoral pro-inflammatory ATMs than omnivores (3.6 ± 2.8 vs. 7.9 ± 4.4 per 100 adipocytes, respectively; P = 0.02). Omnivores had 50% greater (P = 0.01) expression of TNF mRNA in abdominal fat. We found no significant between group differences in muscle ceramide concentrations. CONCLUSIONS: Although the sample size is small, these results may indicate that dietary patterns play a role in adipose tissue inflammation, as reflected by reduced number of femoral ATMs in obese vegetarians than obese omnivores.

Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content.

OBJECTIVE: The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ATM markers. METHODS: A new software program (AMCounter) was evaluated to help measure ATM using IHC, and this was compared to flow cytometry and RT-PCR. RESULTS: IHC had good intraindividual reproducibility for total (CD68), proinflammatory (CD14), and anti-inflammatory (CD206) ATM. The AMCounter improved interreader agreement and was more time efficient. Flow cytometry had acceptable intraindividual reproducibility for the percentage of CD68+ cells that were CD14+ or CD206+ , but not for ATMs per gram of tissue. ATMs per gram of tissue was much greater using IHC than flow cytometry. The flow cytometry and IHC measures of ATM from the same biopsies were not correlated. There were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and CD206 ATMs per 100 adipocytes. Also of interest were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and adipose flow cytometry measures of CD68+ , CD68+ /CD14+ , and CD68+ /CD206+ ATMs per gram of tissue. CONCLUSIONS: The AMCounter software helps provide reproducible and efficient measures of IHC ATMs. Flow cytometry, IHC, and RT-PCR measures of adipose inflammation provide somewhat different information.

Very-long-chain ω-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial.

Background: Increased omega-3 (n-3) fatty acid consumption is reported to benefit patients with metabolic syndrome, possibly due to improved adipose tissue function.Objective: We tested the effects of high-dose, very-long-chain ω-3 fatty acids on adipose tissue inflammation and insulin regulation of lipolysis.Design: A double-blind, placebo-controlled study compared 6 mo of 3.9 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/d (4.2 g total ω-3/d; n = 12) with a placebo (4.2 g oleate/d; n = 9) in insulin-resistant adults. Before and after treatment, the volunteers underwent adipose tissue biopsies to measure the total (CD68+), pro- (CD14+ = M1), and anti- (CD206+ = M2) inflammatory macrophages, crown-like structures, and senescent cells, as well as a 2-step pancreatic clamping with a [U-13C]palmitate infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).Results: In the ω-3 group, the EPA and DHA contributions to plasma free fatty acids increased (P = 0.0003 and P = 0.003, respectively), as did the EPA and DHA content in adipose tissue (P < 0.0001 and P < 0.0001, respectively). Despite increases in adipose and plasma EPA and DHA in the ω-3 group, there were no significant changes in the IC50(palmitate)f (19 ± 2 compared with 24 ± 3 µIU/mL), adipose macrophages (total: 31 ± 2/100 adipocytes compared with 33 ± 2/100 adipocytes; CD14+: 13 ± 2/100 adipocytes compared with 14 ± 2/100 adipocytes; CD206+: 28 ± 2/100 adipocytes compared with 29 ± 3/100 adipocytes), crown-like structures (1 ± 0/10 images compared with 1 ± 0/10 images), or senescent cells (4% ± 1% compared with 4% ± 1%). There were no changes in these outcomes in the placebo group.Conclusions: Six months of high-dose ω-3 supplementation raised plasma and adipose ω-3 fatty acid concentrations but had no beneficial effects on adipose tissue lipolysis or inflammation in insulin-resistant adults. This trial was registered at clinicaltrials.gov as NCT01686568.

How to Measure Adipose Tissue Insulin Sensitivity.

CONTEXT AND OBJECTIVE: Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). DESIGN AND PARTICIPANTS: We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. RESULTS: Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, -0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001). CONCLUSION: Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

More insights into a human adipose tissue GPAT activity assay.

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We recently published findings based on the glycerol 3-phosphate acyltransferase (GPAT) enzyme activity assay we optimized for use with human adipose tissue. These findings include a decrease in total GPAT and GPAT1 as a function of adipocyte size in both omental and subcutaneous adipose tissue and a strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots and between these storage factors and palmitate storage rates into TAG. The aim of this commentary is to expand upon the data from our recent publication. We describe here additional details on the optimization of the GPAT enzyme activity assay, a correlation between DGAT and percentage palmitate in the diacylglycerol fraction, and sex differences in fatty acid storage factors and storage rates into TAG at high palmitate concentrations.

Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity.

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental (r = -0.71, P = 0.003) and subcutaneous (r = -0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots (r values 0.58-0.91) and between these storage factors and palmitate storage rates into TAG (r values 0.55-0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated.

The Rapalogue, CCI-779, improves salivary gland function following radiation.

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.

Autophagy correlates with maintenance of salivary gland function following radiation.

The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6-8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer.