Although obesity is typically associated with metabolic dysfunction and cardiometabolic diseases, some people with obesity are protected from many of the adverse metabolic effects of excess body fat ...and are considered "metabolically healthy." However, there is no universally accepted definition of metabolically healthy obesity (MHO). Most studies define MHO as having either 0, 1, or 2 metabolic syndrome components, whereas many others define MHO using the homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, numerous people reported as having MHO are not metabolically healthy, but simply have fewer metabolic abnormalities than those with metabolically unhealthy obesity (MUO). Nonetheless, a small subset of people with obesity have a normal HOMA-IR and no metabolic syndrome components. The mechanism(s) responsible for the divergent effects of obesity on metabolic health is not clear, but studies conducted in rodent models suggest that differences in adipose tissue biology in response to weight gain can cause or prevent systemic metabolic dysfunction. In this article, we review the definition, stability over time, and clinical outcomes of MHO, and discuss the potential factors that could explain differences in metabolic health in people with MHO and MUO - specifically, modifiable lifestyle factors and adipose tissue biology. Better understanding of the factors that distinguish people with MHO and MUO can produce new insights into mechanism(s) responsible for obesity-related metabolic dysfunction and disease.
Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and ...de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low‐density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity. (HEPATOLOGY 2009.)
Racial stereotypes are commonly activated by informational cues that are detectable in people's faces. Here, we used a sequential priming task to examine whether and how the salience of emotion ...(angry/scowling vs. happy/smiling expressions) or apparent race (Black vs. White) information in male face primes shapes racially biased weapon identification (gun vs. tool) decisions. In two experiments (N
= 546) using two different manipulations of facial information salience, racial bias in weapon identification was weaker when the salience of emotion expression versus race was heightened. Using diffusion decision modeling, we tested competing accounts of the cognitive mechanism by which the salience of facial information moderates this behavioral effect. Consistent support emerged for an initial bias account, whereby the decision process began closer to the "gun" response upon seeing faces of Black versus White men, and this racially biased shift in the starting position was weaker when emotion versus race information was salient. We discuss these results vis-à-vis prior empirical and theoretical work on how facial information salience moderates racial bias in decision-making.
In this article, we describe four theoretical and methodological problems that have impeded implicit attitude research and the popular understanding of its findings. The problems all revolve around ...assumptions made about the relationships among measures (indirect vs. versus direct), constructs (implicit vs. explicit attitudes), cognitive processes (e.g., associative vs. propositional), and features of processing (automatic vs. controlled). These assumptions have confused our understandings of exactly what we are measuring, the processes that produce implicit evaluations, the meaning of differences in implicit evaluations across people and contexts, the meaning of changes in implicit evaluations in response to intervention, and how implicit evaluations predict behavior. We describe formal modeling as one means to address these problems, and provide illustrative examples. Clarifying these issues has important implications for our understanding of who has particular implicit evaluations and why, when those evaluations are likely to be particularly problematic, how we might best try to change them, and what interventions are best suited to minimize the effects of implicit evaluations on behavior.
Background: Age-associated declines in muscle mass and function are major risk factors for an impaired ability to carry out activities of daily living, falls, prolonged recovery time after ...hospitalization, and mortality in older adults. New strategies that can slow the age-related loss of muscle mass and function are needed to help older adults maintain adequate performance status to reduce these risks and maintain independence. Objective: We evaluated the efficacy of fish oil–derived n–3 (ω -3) PUFA therapy to slow the age-associated loss of muscle mass and function. Design: Sixty healthy 60–85-y-old men and women were randomly assigned to receive n–3 PUFA (n = 40) or corn oil (n = 20) therapy for 6 mo. Thigh muscle volume, handgrip strength, one-repetition maximum (1-RM) lower- and upper-body strength, and average power during isokinetic leg exercises were evaluated before and after treatment. Results: Forty-four subjects completed the study 29 subjects (73%) in the n–3 PUFA group; 15 subjects (75%) in the control group. Compared with the control group, 6 mo of n–3 PUFA therapy increased thigh muscle volume (3.6%; 95% CI: 0.2%, 7.0%), handgrip strength (2.3 kg; 95% CI: 0.8, 3.7 kg), and 1-RM muscle strength (4.0%; 95% CI: 0.8%, 7.3%) (all P < 0.05) and tended to increase average isokinetic power (5.6%; 95% CI: −0.6%, 11.7%; P = 0.075). Conclusion: Fish oil–derived n–3 PUFA therapy slows the normal decline in muscle mass and function in older adults and should be considered a therapeutic approach for preventing sarcopenia and maintaining physical independence in older adults. This study was registered at clinicaltrials.gov as NCT01308957.
People sometimes prefer groups to which they do not belong (outgroups) over their own groups (ingroups). Many long-standing theoretical perspectives assume that this outgroup favorability bias ...primarily reflects negative ingroup evaluations rather than positive outgroup evaluations. To examine the contributions of negative ingroup versus positive outgroup evaluations to outgroup bias, we examined participants’ data (total
n
> 879,000) from Implicit Association Tests A. G. Greenwald, D. E. McGhee, J. L. K. Schwartz,
J. Pers. Soc. Psychol.
74, 1464–1480 (1998) measuring intergroup attitudes across four social domains in exploratory and preregistered confirmatory analyses. Process modeling F. R. Conrey, J. W. Sherman, B. Gawronski, K. Hugenberg, C. J. Groom,
J. Pers. Soc. Psychol.
89, 469–487 (2005) was applied to the responses of participants who demonstrated implicit outgroup bias to separately estimate the contributions of negative ingroup and positive outgroup evaluations. The outgroup biases of lower-status group members (i.e., Asian, Black, gay and lesbian, and older people) consistently reflected greater contributions of positive outgroup evaluations than negative ingroup evaluations. In contrast, the outgroup biases of higher-status group members (i.e., White, straight, and younger people) reflected a more varied pattern of evaluations. We replicated this pattern of results using explicitly measured intergroup evaluations. Taking these data together, the present research demonstrates a positive–negative asymmetry effect of outgroup bias, primarily among members of lower-status groups.
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD
) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a ...rate-limiting factor in mammalian NAD
biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR) increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly ...releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of “inter-organ mitohormesis.” Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity.
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•Mitochondrial stress stimulates adipocyte sEV release•Adipocyte stress-induced sEVs are enriched with oxidatively damaged mitochondria•Mitochondria in sEVs from stressed adipocytes induce a burst of ROS in cardiac tissue•The adipocyte-derived pro-oxidant signal protects the heart through hormesis
Crewe et al. report that adipocytes release sEVs containing damaged mitochondria in response to energetic stress, such as seen in chronic obesity. The sEV-associated mitochondria induce transient mitochondrial oxidative stress in cardiac tissue, resulting in an antioxidant response. Adipocyte sEVs thereby precondition the heart to protect against ischemia/reperfusion injury.
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