Onset Of Obesity Research Articles

Identification of sensitive periods of weight status transition over the lifespan in Chinese population

BackgroundThe prevalence of high body mass index (BMI) is increasing in both children and adults worldwide. However, it is unclear whether vulnerabilities to maintenance and transition of weight status vary throughout the lifespan.ObjectiveWe aimed to characterize dynamic transitions of weight statuses across different life stages and to identify the sensitive periods for maintenance, onset, and resolution of obesity.MethodsThis longitudinal study included a total of 23,179 participants aged 6–80 years with 95,994 BMI measurements from the China Health and Nutrition Survey 1989–2015. To examine the heterogeneity in transitions of weight statuses across different life stages, we divided participants into 8 sub-cohorts based on baseline ages by 10-year intervals, i.e., 6–10 years, 11–20 years, 21–30 years, 31–40 years, 41–50 years, 51–60 years, 61–70 years, and 71–80 years. We estimated the probabilities of transitioning between weight statuses at a given follow-up year by baseline age using generalized linear mixed-effects models.ResultsThe predicted prevalence of obesity decreased from 6 years, bottomed at around 20 years, increased thereafter, peaked at around 55 years, and then decreased gradually. In general, participants with underweight had lower probabilities of maintaining the same status compared to those with normal weight, overweight, or obesity for all age groups. For 10-year follow-up, individuals aged 21–30 years had the highest probabilities of transitioning from normal weight to obesity and transitioning from overweight to obesity compared to those in other age groups. Individuals aged 6–20 years had the highest probabilities of transitioning from obesity to normal weight and transitioning from overweight to normal weight. Individuals in all adult age groups had higher probabilities of maintaining obesity status than children and adolescents.ConclusionsYoung adulthood is the most sensitive period for obesity onset, whereas childhood and adolescence are the most sensitive periods for obesity resolution. The findings suggest the heterogeneity of susceptibilities to weight status transitions across different life stages and highlight the importance of the development of age-appropriate approaches for the prevention and intervention of obesity.

Assessment of basic locomotor movement skills of elementary school students using TGMD-2

Introduction. Basic movement is the foundation of human behavior and helps young children to learn new skills in other areas. A child can actively move and exercise if they have basic movement skills. Therefore, it is necessary to identify the real condition of children’s movement skills, especially lower grade elementary school children. This can be used as a reference to prevent undesirable outcomes, such as the onset of obesity in children. Method. This study is a Pre-experimental design conducted to assess basic movement abilities in learning activities of eight locomotor movements, namely walking, running, hopping, jumping, galloping, sliding, skipping, and leaping by means of observation through motion observation instruments using the Gross Motor Development 2 (TGMD-2) Test approach.The subjects of this study were 42 students from Pilahan public elementary school, including 14 students from grade 1, 14 from grade 2, and 14 from grade 3. Results. The research found that among the 42 lower grade students of Pilahan State Elementary School, 12 students scored below average, 14 students scored moderately, and 16 students scored above average. Conclusion. Thus, it is expected that this data can be used as a basis for evaluating students who have not scored above average. This data is also expected to serve as a reference for further research on the issue of lower grade elementary school students with below-average basic movement skills.

Progress in Improving Metabolic Syndrome with Adzuki Bean

Metabolic syndrome (MS) is a clinical condition characterized by the simultaneous onset of abdominal obesity, abnormal blood sugar levels, dyslipidemia, and hypertension. It significantly impacts overall health and exhibits an increasing prevalence with a decreasing age of onset. Metabolic syndrome affects approximately one quarter of the global population, posing a critical threat to human well-being as a major public health concern. Current approaches for prevention and management primarily rely on pharmaceutical interventions or lifestyle modifications; however, their effectiveness remains limited. In recent years, the concept of food-medicine homology has emerged as a novel theory that holds promise in alleviating metabolic syndrome. Adzuki bean, a widely cultivated legume rich in various nutrients and bioactive compounds, has been traditionally recognized in Chinese medicine for its beneficial effects on invigorating QI (vital energy), arming the middle (digestive system), strengthening the spleen (immune function), and eliminating dampness (excess moisture). Numerous studies have demonstrated that adzuki bean can effectively regulate blood sugar levels, lipid profiles, blood pressure while improving gut microbiota imbalances and exhibiting anti-obesity properties to some extent. As such, it can serve as an adjunct therapy for managing metabolic syndrome. Compared to conventional drugs used for this purpose, adzuki bean offers safer alternatives with diverse product options. These findings provide valuable theoretical foundations and practical references for preventing and treating diseases associated with metabolic syndrome.

Are labor epidural catheters after a combined spinal epidural (CSE) technique more reliable than after a traditional epidural? A retrospective review of 9153 labor epidural catheters.

The combined spinal epidural (CSE) technique may associate with a lower failure rate of epidural catheters compared to traditional epidural catheters. This may be significant for the parturients as failure of neuraxial analgesia has been associated with a negative impact on birth experience. In this one-year retrospective study, the failure rate of epidural catheters was compared between 3201 and 5952 epidural catheters after initiation of neuraxial analgesia by the CSE or traditional epidural technique, respectively. Parturient background information, labor parameters, and neuraxial interventions were collected from 9153 parturients. Failure was defined as replacement of a used epidural catheter by new regional analgesia procedures or general anesthesia during intrapartum cesarean delivery. The primary outcome was the failure rate of epidural catheters. The secondary outcome was the time from the initial analgesia intervention to the epidural catheter replacement and progression of labor during this time. The CSE method was used at an earlier stage of labor, and the parturients were more often primiparous and undergoing induced labor. Earlier onset of analgesia, obesity, induced labor, anesthesiologist experience, and cesarean delivery were found to be significant cofactors for catheter failure. The unadjusted failure rate was 168/3201 (5.2%) and 223/5952 (3.7%) (OR 1.42 [1.16-1.75]) after initiation of analgesia by CSE or traditional epidural method. After controlling for the stage of labor, body mass index, induction of labor, and anesthesiologist's experience level, the adjusted OR for epidural catheter replacement was 1.04 (0.83-1.29) p = .736. The mean (SD) time until epidural catheter failure was 6.3 (4.4) and 4.0 (4.1) hours following initiation of analgesia by CSE or traditional epidural technique, respectively (p < .001). Cervical dilatation progressed from 4.3 (1.4) to 6.4 (2.1) cm and 5.1 (1.5) to 6.7 (1.7) cm between primary neuraxial analgesia and epidural catheter replacement. CSE technique was not associated with a better survival rate of epidural catheters for provision of analgesia or epidural top-up anesthesia for intrapartum CD. In addition, the time to replacement of the catheter was significantly longer when analgesia was initiated with the CSE technique. Maternal satisfaction scores were lower if catheters required replacement.

Amino acid is a major carbon source for hepatic lipogenesis

Increased de novo lipogenesis is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) in obesity, but the macronutrient carbon source for over half of hepatic fatty acid synthesis remains undetermined. Here, we discover that dietary protein, rather than carbohydrates or fat, is the primary nutritional risk factor for MASLD in humans. Consistently, exvivo tracing studies identify amino acids as a major carbon supplier for the tricarboxylic acid (TCA) cycle and lipogenesis in isolated mouse hepatocytes. Invivo, dietary amino acids are twice as efficient as glucose in fueling hepatic fatty acid synthesis. The onset of obesity further drives amino acids into fatty acid synthesis through reductive carboxylation, while genetic and chemical interventions that divert amino acid carbon away from lipogenesis alleviate hepatic steatosis. Finally, low-protein diets (LPDs) not only prevent body weight gain in obese mice but also reduce hepatic lipid accumulation and liver damage. Together, this study uncovers the significant role of amino acids in hepatic lipogenesis and suggests a previously unappreciated nutritional intervention target for MASLD.

The Enigma That Is ROHHAD Syndrome: Challenges and Future Strategies

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare syndrome presenting in early childhood associated with a high risk of mortality between 50 and 60%. It is characterised by rapid, early onset of obesity between 1.5–7 years, along with central hypoventilation and hypothalamic dysfunction, such as central hypothyroidism, hyperprolactinemia, disorders of sodium and water balance, growth hormone deficiency, adrenocortical insufficiency, or disorders of puberty and features of autonomic dysregulation. Up to half of cases have neural crest tumours, most commonly ganglioneuromas or ganglioneuroblastomas. The incidence of ROHHAD syndrome in any population is unknown. Currently, there is no specific diagnostic or genetic biomarker for ROHHAD, and diagnosis is based on clinical signs and symptoms, which is often challenging, and consequently may be delayed or unrecognised. Early diagnosis is important, as without intervention, ROHHAD is associated with high morbidity and mortality. Aetiology remains unclear; an autoimmune origin has been postulated, with immunosuppressive agents being used with variable benefit. With no cure, multidisciplinary management is largely supportive. Therefore, there are many unanswered questions in ROHHAD syndrome. In this review article, we outline the challenges posed by ROHHAD syndrome, including aetiology, genetics, diagnosis, screening, management, and prognosis. We present research priorities to tackle these issues to improve outcomes.

Origins of obesity in the womb: Fetal adiposity and its determinants.

Birth weight is an important predictor of perinatal complications and long-term health outcomes of offspring. Fetal programming influenced by maternal obesity, overnutrition, and hyperglycemia has been proposed as the fuel overload hypothesis. Recent investigations related with fetal body composition have revealed that neonatal adiposity can be predicted by fetal fat mass, and that maternal insulin resistance and serum leptin level are indicators of fetal adiposity. Based on the current evidence, the origins of obesity can partly be traced back into the fetal life. Further clarification of the determinants of fetal fat mass may lead to the clinical interventions and treatment strategies for fetal growth and development. This effort potentially leads to the elucidation of pathological conditions related with long-term health outcomes and the primary prevention of childhood obesity and early onset metabolic syndrome.

Socioeconomic Status and Obesity.

Obesity is a pervasive public health problem that causes debilitating complications across the life course. One opportunity for preventing the onset of obesity is to focus on its social determinants. Socioeconomic status (SES), which includes factors such as income, educational attainment, occupational prestige, and access to resources, is a key determinant of obesity. In this scoping mini-review, we summarized review articles and meta-analyses of the SES-obesity association. From the 1980s to the present, cross-sectional studies have demonstrated a persistent socioeconomic gradient in obesity in which the association is negative in developed countries and positive in developing countries. Longitudinal studies have revealed the bidirectionality of the SES-obesity association; some studies demonstrate that socioeconomic adversity precedes the onset of obesity, while others provide evidence of reverse causality. While earlier studies relied on anthropometric assessments of weight and height to define obesity, the use of modern technologies like dual-energy x-ray absorptiometry and bioelectrical impedance have demonstrated that the socioeconomic gradient in obesity is robust across multiple indicators of body composition, including direct measures of lean and fat mass. More recently, examination of mediators and moderators of the SES-obesity association have highlighted causal pathways and potential intervention targets, with a focus on health behaviors, environmental conditions, psychological factors, and biological processes. We describe current gaps in knowledge and propose opportunities for future innovation to reduce the burden of obesity and related socioeconomic disparities.

Non-communicable diseases: Opportunities to promote future health during the first 1000 day of life

The Developmental Origins of Health and Disease (DOHaD) framework now underlies the evolution and epigenetics of many non-communicable diseases that develop in adult life. Type 2 diabetes, obesity, hypertension, heart disease and stroke in particular have links back to events during the first 1000 days of life, and as the world is witnessing an epidemic of these conditions, identifying measures able to contribute to reducing the potential for these NCDs to develop in our aging populations becomes all the more important. Parental health at conception and good maternal health and nutrition throughout pregnancy are known to be integral to normal infant development and health in later life, but more recently the central importance of infant nutrition that achieves healthy weight gain has become recognized. In this context, achieving growth patterns for infants that avoid either the onset of obesity or development of stunting during the first 1000 days of life appears to be an achievable goal with significant potential for the avoidance of many NCDs in later life. Hence the relevance of health promotion initiatives to share this knowledge among health care providers and educate parents on the benefits of optimal infant nutrition.

Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead.

Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.

Apparent Saturation of Branched-Chain Amino Acid Catabolism After High Dietary Milk Protein Intake in Healthy Adults

Abstract Context Milk protein contains high concentrations of branched-chain amino acids (BCAA) that play a critical role in anabolism and are implicated in the onset of obesity and chronic disease. Characterizing BCAA catabolism in the postprandial phase could elucidate the impact of protein intake on obesity risk established in the “early protein hypothesis.” Objective To examine the acute effects of protein content of young child formulas as test meals on BCAA catabolism, observing postprandial plasma concentrations of BCAA in relation to their degradation products. Methods The TOMI Add-On Study is a randomized, double-blind crossover study in which 27 healthy adults consumed 2 isocaloric young child formulas with alternating higher (HP) and lower (LP) protein and fat content as test meals during separate interventions, while 9 blood samples were obtained over 5 hours. BCAA, branched-chain α-keto acids (BCKA), and acylcarnitines were analyzed using a fully targeted HPLC-ESI-MS/MS approach. Results Mean concentrations of BCAA, BCKA, and acylcarnitines were significantly higher after HP than LP over the 5 postprandial hours, except for the BCKA α-ketoisovalerate (KIVA). The latter metabolite showed higher postprandial concentrations after LP. With increasing mean concentrations of BCAA, concentrations of corresponding BCKA, acylcarnitines, and urea increased until a breakpoint was reached, after which concentrations of degradation products decreased (for all metabolites except valine and KIVA and Carn C4:0-iso). Conclusion BCAA catabolism is markedly influenced by protein content of the test meal. We present novel evidence for the apparent saturation of the BCAA degradation pathway in the acute postprandial phase up to 5 hours after consumption.

Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial.

The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 33%, absolute risk difference = -27%, 95% CI -41% to -12%, p < 0.001; number needed to treat 3, 95% CI 2 to 8, intention to treat analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the CT and MD mothers, respectively (p < 0.0001). MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.

Protocol for the LIFEH project: a prospective observational study to explore lifestyle among people living with HIV experiencing weight gain, looking beyond antiretroviral therapy

IntroductionWeight gain, together with the onset of overweight and obesity, is a relevant emerging health issue among people living with HIV (PLWH). A large body of literature recognises this issue...

Male infertility and obesity.

The increasing rate of obesity is having an adverse impact on male reproduction. The negative effect of reactive oxygen species on male reproductive tissues and the age of onset of obesity are new areas of research on male infertility. This review highlights how obesity impairs male reproduction through complex mechanisms, including metabolic syndrome, lipotoxicity, sexual dysfunction, hormonal and adipokine alterations as well as epigenetic changes, and how new management strategies may improve the reproductive health of men throughout life.

Follicle-stimulating hormone receptor gene polymorphisms influence Body Mass Index, metabolism, and bone mineral density in postmenopausal women.

Covering a significant part of a woman's life, the postmenopausal phase is often associated with the onset of obesity, metabolic dysfunction, osteoporosis, and their most disabling complications. In this context, scant evidence from both preclinical and clinical studies suggests that single nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHR) gene might be involved in the etiopathogenesis of these conditions, posing them as possible molecular predictors of their development. Therefore, this study aimed to evaluate the role of the FSHR gene SNPs c.2039A>G and c.-29 G>A on Body Mass Index (BMI), metabolic parameters, and bone metabolism in postmenopausal women. To achieve this goal, 49 postmenopausal Caucasian women aged from 45 to 80 years and with no factors known to influence metabolism and/or bone mineral density (BMD) were enrolled and assessed for their medical history, medical family history, anthropometric parameters and hormonal, metabolic and lipid profiles, and BMD. Then, they were genotyped for the FSHR gene SNPs c.2039A>G and c.-29G>A. Finally, the resulting data were classified according to woman's genotypes and subjected to statistical analysis. No significant differences were found between the distributions of most endpoint parameters examined by genotype. However, none of the women with the c.2039A>G FSHR GG gene SNP were affected by obesity and had the highest lumbar BMD z-score within the cohort. Additionally, those with the FSHR c.-29G>A AA genotype had the lowest serum glucose levels. This preliminary study suggests that the FSHR c.2039A>G GG SNP, which is associated with reduced sensitivity of the FSHR, may have a protective role against obesity, offering further evidence for the possible association among FSH, FSHR polymorphisms, and insulin metabolism.

Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns1. Here we uncover the mechanism by which NPY in sympathetic neurons2,3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY+ sympathetic axons are a smallersubset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation ofmural cells, which are a source of thermogenic adipocytes in both BAT and WAT4-6. We found that diet-induced obesity leads to neuropathy of NPY+ axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapularBAT, reducing itsthermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.

Cordycepin Ameliorates High Fat Diet-Induced Obesity by Modulating Endogenous Metabolism and Gut Microbiota Dysbiosis.

Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.

Adipose tissue macrophage infiltration and hepatocyte stress increase GDF-15 throughout development of obesity to MASH

Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15. Inactivation of Gdf15 in macrophages reduces plasma GDF-15 concentrations and exacerbates obesity in mice. During MASH development, Gdf15 expression additionally increases in hepatocytes through stress-induced TFEB and DDIT3 signaling. Together, these results demonstrate a dual contribution of AT and liver to GDF-15 production in metabolic diseases and identify potential therapeutic targets to raise endogenous GDF-15 levels.

Clarifying main nutritional aspects and resting energy expenditure in children with Smith-Magenis syndrome

Our study aims to define resting energy expenditure (REE) and describe the main nutritional patterns in a single-center cohort of children with Smith-Magenis syndrome (SMS). REE was calculated using indirect calorimetry. Patients’ metabolic status was assessed by comparing measured REE (mREE) with predictive REE (pREE). Patients also underwent multidisciplinary evaluation, anthropometric measurements and an assessment of average energy intake, using a 3-day food diary, which was reviewed by a specialized dietitian. Twenty-four patients (13 M) were included, the median age was 9 years (IC 95%, 6–14 years), 84% had 17p11.2 deletion, and 16% had RAI1 variants. REE was not reduced in SMS pediatric patients, and the mREE did not differ from the pREE. In patients with RAI1 variants (16%, n = 3/24), obesity was more prevalent than those with 17p11.2 deletion (100% vs 38%). Lower proteins intake and higher total energy intake were reported in obese and overweight patients, compared to healthy weight children. No significant difference was found between males and females in energy or macronutrient intake. Conclusions: In SMS, the onset of obesity is not explained by REE abnormalities, but dietary factors seem to be crucial. Greater concern should be addressed to patients with RAI1 variants. A better understanding of the molecular mechanisms causing obesity in SMS patients could set the basis for possible future targeted therapies.What is Known:• More than 90% of SMS patients after the age of 10 are overweight or obese.What is New:• Onset of overweight and obesity in SMS pediatric patients is not explained by abnormal resting energy expenditure.• The development of syndrome-specific dietary guidelines for SMS patients should be of utmost relevance and are highly needed.

Type 2 diabetes: a sacrifice program handling energy surplus

Abstract Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss. The body employs three adaptive strategies in response to energy surplus: the first one is adipose tissue expansion to store the energy for weight gain under normal weight conditions; the second one is insulin resistance to slow down adipose tissue expansion and weight gain under overweight conditions; and the third one is the onset of T2DM following β cell failure to reverse the weight gain in obese conditions. The primary signaling molecules driving the compensatory responses are adenosine derivatives, such as adenosine triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), and reduced nicotinamide adenine dinucleotide (NADH). These molecules exert their effects through allosteric, post-translational, and transcriptional regulation of metabolic pathways. The insights suggest that insulin resistance and T2DM are protective mechanisms in the defense against excessive adiposity to avert severe obesity. The perspective provides a unified framework explaining the interactions between the two diseases and opens new avenues in the study of T2DM.