Metabolically healthy obesity:Is it really healthy for type 2 diabetes mellitus?

Metabolically healthy obese(MHO)individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome.However,the association between MHO and type 2 diabetes(T2DM)is still controversial.Some studies indicated that MHO is a favorable phenotype for T2DM,but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normalweight individuals,especially among those who would acquire metabolically unhealthy obesity.This has been supported by finding insulin resistance and lowgrade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction.Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO.Here,we reviewed current literature on the relationship between MHO and T2DM,discussed the determinants for the development of diabetes in MHO,and summarized the measures for the prevention of T2DM in MHO.

Comparative Study of Inflammatory and Oxidative Stress Biomarkers in Different Metabolically Healthy Obesity Phenotypes

Aims: Obesity is the major contributor of the metabolic syndrome (MetS), but a unique phenotype of obesity known as metabolically healthy obese (MHO) shows healthier metabolic profile; however understanding of their biochemical correlates is poorly understood. Obesity is defined by Body mass index (BMI), but controversy exists regarding ethnic-specific BMI cut-offs. The present study used the Asian Indian BMI cut-offs to assess relationships of MHO phenotypes with oxidative stress (OS) and inflammation. Methods: In this case-control study, 299 metabolically-healthy (MH) respondents were divided into four groups as per Asian criteria for obesity: MH non-obese (MHNO), MH overweight (MHOW), MHO and MH severely obese (MHSO). Their oxidative stress and pro-inflammatory markers were measured. Results: Levels of hydroxyl radicals (·OH), fluorescent oxidation products (FLOP), MDA, PCO and inflammatory markers CRP, TNF-α, IL-6 were highest in MHSO phenotype followed by the MHO, MHOW and MHNO groups (p > 0.0001), whereas antioxidant markers, CuZn-SOD, catalase, glutathione peroxidase and total antioxidant activity followed the reverse trend. The MHNO and MHOW groups showed significant difference with regard to (·OH) radicals and FLOP. Moreover, ·OH radicals, FLOP and inflammatory markers were significantly correlated to BMI in MHSO and MHO but not in MHNO and MHOW group. Conclusion: The MHO and MHSO phenotype display differences in terms of OS and inflammatory markers at lower BMI cut-offs, indicating that they may be on the way to becoming “unhealthy” obese. The lower BMI cut-offs proposed by Indian Consensus Group would help in understanding of manifestation of metabolic syndrome.

Obesity,metabolic health and omics:Current status and future directions

The growing obesity epidemic is becoming a major public health concern,and the associated costs represent a considerable burden on societies.Among the most common complications of severe obesity are the development of hypertension,dyslipidemia,type 2 diabetes,cardiovascular disease,and various types of cancer.Interestingly,some obese individuals have a favorable metabolic profile and appear to be somehow protected from the detrimental effects of excessive adipose tissue accumulation.These individuals remain normoglycemic,insulin sensitive,and hypotensive with proper blood lipid levels,despite their high body mass index and/or waist circumference.Multiple independent observations have led to the concept of the metabolically healthy obese(MHO) phenotype,yet no consensus has been reached to date regarding a universal definition or the main mechanism behind this phenomenon.Recent technological advances and the use of high-throughput analysis techniques have revolutionized different areas of biomedical research.A multi-omics approach,which is used to investigate changes at different molecular levels in an organism or tissue,may provide valuable insights into the interplay between the molecules or pathways and the roles of different factors involved in the mechanisms underlying metabolic health deterioration.The aim of this review is to present the current status regarding the use of omics technologies to investigate the MHO phenotype,as well as the results of targeted analyses conducted in MHO individuals.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain elusive.Rab18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and maturation.In the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice.Rab18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype mice.When subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in SAT.In contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic inflammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid toxicity.Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT.In conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Prediction of Metabolic Disorders Using NMR-Based Metabolomics:The Shanghai Changfeng Study

A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of life.We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future.Participants were divided into metabolically healthy overweight/obesity(MHO)and meta-bolically healthy normal weight(MHNW)groups according to their body mass index(BMI)and metabolic status.Their serum metabolomic profile was measured using a ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR).The prevalence of diabetes,hypertriglyceridemia,hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline.After a median of 4.2 years of follow-up,more MHO participants became metabolically unhealthy than MHNW participants.However,a subgroup of MHO participants who remained metabolically healthy(MHO→MHO)had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination,despite a signifi-cant reduction in their serum concentrations of high-density lipoprotein(HDL)and an elevation in valine,leucine,alanine and tyrosine.Further correlation analysis indicated that serum intermediate-density lipoprotein(IDL)and very low-density lipoprotein cholesterol(VLDL-CH)might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.