Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history

Abstract Background/objectives Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. Subjects/methods 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points. Results Circulating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5–4.9) vs. 3.8 (3.2–4.6) µg/ml; p = 2.1 × 10−5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = −0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B. Conclusions Our data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes. Trial registration ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.

Download Full-text

Metabolically healthy obesity: what's in a name?

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz133 ◽

2019 ◽

Vol 110 (3) ◽

pp. 533-539 ◽

Cited By ~ 19

Author(s):

Faidon Magkos

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Visceral Adipose Tissue ◽

Liver Fat ◽

Metabolically Healthy Obesity ◽

Liver Fat Content ◽

Metabolically Healthy ◽

Visceral Adipose

ABSTRACT Metabolically healthy obesity refers to an obesity phenotype with no or little evidence of metabolic dysfunction. Lower liver fat content and visceral adipose tissue, greater insulin sensitivity and secretion, greater cardiorespiratory fitness, and a predominantly lower body (i.e., leg) fat deposition are key physiological traits of a metabolically healthy phenotype. About 35% of all subjects with obesity are metabolically healthy. These individuals have approximately half the risk of developing type 2 diabetes and cardiovascular disease compared with metabolically unhealthy subjects with obesity, but they still have a significantly greater risk (by 50–300%) compared with metabolically healthy lean subjects. Therefore, absence of metabolic risk factors in people with obesity should not be a contraindication for weight-loss treatment. Metabolically healthy obesity needs to be treated, and this need is reinforced by the fact that this phenotype is not stable over time, as ∼50% of these subjects will cease being metabolically healthy within ∼10 y. Intervening early is therefore important. Weight loss dose-dependently decreases visceral adipose tissue and liver fat content, and it improves multiorgan insulin sensitivity and β-cell function (i.e., it beneficially affects many of the physiological traits of a metabolically healthy phenotype); however, weight loss is very difficult to maintain. This typically results in disappointment among patients and hinders adherence, which is likely critical for the limited success of most weight-loss treatments in the long term. On the other hand, using ≥1 metabolic health targets in a non-weight-loss-centered treatment paradigm that includes prudent dietary changes and increased physical activity can serve as an appropriate first goal that can help motivate patients toward the long-term goals of obesity treatment.

Download Full-text

Family support and weight-loss strategies among adolescents reporting sustained weight loss

Public Health Nutrition ◽

10.1017/s1368980012002820 ◽

2012 ◽

Vol 16 (3) ◽

pp. 499-504 ◽

Cited By ~ 3

Author(s):

Jennifer Utter ◽

Simon Denny ◽

Robyn Dixon ◽

Shanthi Ameratunga ◽

Tasileta Teevale

Keyword(s):

Weight Loss ◽

New Zealand ◽

Young People ◽

Family Support ◽

Weight Control ◽

Control Strategies ◽

Sustained Weight Loss ◽

No Weight Loss ◽

Weight Control Strategies

AbstractObjectiveThe current research aims to describe the weight-control strategies and family support for young people reporting sustained weight loss in a large, population-based sample.DesignData were collected as part of Youth'07, a nationally representative survey of the health and well-being of New Zealand youth.SettingNew Zealand secondary schools, 2007.SubjectsSecondary-school students (n 9107).ResultsAmong young people who attempted weight loss in the previous year, 51 % reported long-term weight loss (lost weight and maintained weight loss for 6 months). Students reporting long-term weight loss were more likely to be male, but did not differ by age, ethnicity, socio-economic deprivation or measured weight status from students who reported temporary/recent weight loss or no weight loss. Students with long-term weight loss also reported healthier weight-control strategies (e.g. exercising, eating fewer fatty foods, eating fewer sweets), high parental support for healthy eating/activity and were less likely to report being teased about their weight by their family and having junk food available at home than students with temporary/recent weight loss or no weight loss.ConclusionsApproximately 50 % of young people attempting weight loss reported sustained weight loss. Young people who reported sustained weight loss appeared to have more family support than those who did not achieve this, suggesting the importance for weight-control services and interventions in adolescents of actively engaging the family.

Download Full-text

Effects of Weight Loss on Adipose and Muscular Neuropilin 1 mRNA Expression in Obesity: Potential Implication in SARS-CoV-2 Infections?

Obesity Facts ◽

10.1159/000520419 ◽

2021 ◽

pp. 1-9

Author(s):

Dominik Soll ◽

Finja Beer ◽

Leonard Spranger ◽

Linna Li ◽

Joachim Spranger ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Mrna Expression ◽

Neuropilin 1 ◽

Before And After ◽

Short And Long Term

Introduction: Neuropilin 1 (NRP-1) is a novel co-receptor promoting SARS-CoV-2 infectivity. Animal data indicate a role in trans-endothelial lipid transport and storage. As human data are sparse, we aimed to assess the role of NRP-1 in 2 metabolic active tissues in human obesity and in the context of weight loss-induced short- and long-term metabolic changes. Methods: After a standardized 12-week weight reduction program, 143 subjects (age >18; body mass index ≥27 kg/m2, 78% female) were randomized to a 12-month lifestyle intervention or a control group using a stratified randomization scheme. This was followed by 6-month follow-up without any intervention. Phenotyping was performed before and after weight loss, after 12-month intervention and after subsequent 6 months of follow-up. Tissue-specific insulin sensitivity was estimated by HOMA-IR (whole body and mostly driven by liver), insulin sensitivity index (ISI)Clamp (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1AT) and skeletal muscle (NRP-1SM) before and after weight loss. Results: NRP-1 was highly expressed in adipose tissue (7,893 [7,303–8,536] counts), but neither NRP-1AT nor NRP-1SM were related to estimates of obesity. Higher NRP-1AT was associated with stronger FFASupp (r = −0.343, p = 0.003) and a tendency to higher ISIClamp (r = 0.202, p = 0.085). Weight loss induced a decline of NRP-1AT but not NRP-1SM. This was more pronounced in subjects with stronger reduction of adipose ACE-2 mRNA expression (r = 0.250; p = 0.032) but was not associated with short- and long-term improvement of FFASupp and ISIClamp. Conclusion: NRP-1AT is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1AT seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1AT and ACE-2AT indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.

Download Full-text

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00453.2013 ◽

2014 ◽

Vol 306 (5) ◽

pp. E552-E558 ◽

Cited By ~ 52

Author(s):

Johanne H. Ellenbroek ◽

Laura van Dijck ◽

Hendrica A. Töns ◽

Ton J. Rabelink ◽

Françoise Carlotti ◽

...

Keyword(s):

Weight Loss ◽

Hepatic Steatosis ◽

Glucose Intolerance ◽

Cell Mass ◽

High Fat ◽

Β Cell ◽

The Metabolic Syndrome ◽

No Weight Loss ◽

Low Carbohydrate

High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and β- and α-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1β, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from β-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in β-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also α-cell mass was markedly decreased, resulting in a lower α- to β-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in β- and α-cell mass, but no weight loss. This indicates that long-term high-fat, low-carbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans.

Download Full-text