The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite great efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The risks associated with overweight/obesity are primarily related to the deposition of adipose tissue, which leads to excess adiposity or body fatness. Furthermore, weight loss, specifically loss of body fat, is associated with improvement in obesity-related comorbidities. Before weight loss interventions can be recommended, however, patients must be assessed for their adiposity-related risk. Unfortunately, healthcare providers and systems have not done a good job of assessing for excess adiposity even in its simplest form, such as measuring body mass index (BMI). It is for these reasons that we must emphasize the importance of assessing adiposity in clinical practices. Although it can be argued that the entire population should be targeted as an important public health issue with a goal of prevention of weight gain and obesity, there are currently so many “at risk” individuals that simple strategies to identify and treat those individuals are necessary. We must identify those individuals at highest risk of comorbidities in order to identify those who might benefit the most from aggressive weight management.

This scientific statement will first briefly review the epidemiology of obesity and its related comorbidities, supporting the need for improved assessment of adiposity in daily clinical practice. This will be followed by a discussion of some of the challenges and issues associated with assessing adiposity and then by a review …

Assessing Adiposity A Scientific Statement From the American Heart Association

Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.

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Sex differences in human adipose tissues - the biology of pear shape

Objective

To evaluate the contribution of leptin (an adipose tissue–derived hormone) to the pathophysiology of osteoarthritis (OA), by determining the level of leptin in both synovial fluid (SF) and cartilage specimens obtained from human joints. We also investigated the effect of leptin on cartilage, using intraarticular injections of leptin in rats.



Methods

Leptin levels in SF samples obtained from OA patients undergoing either knee replacement surgery or knee arthroscopy were measured by enzyme-linked immunosorbent assay. In addition, histologic sections of articular cartilage and osteophytes obtained during surgery for total knee replacement were graded using the Mankin score, and were immunostained using antibodies to leptin, transforming growth factor β (TGFβ), and insulin-like growth factor 1 (IGF-1). For experimental studies, various doses of leptin (10, 30, 100, and 300 μg) were injected into the knee joints of rats. Tibial plateaus were collected and processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (Ob-Rb), and growth factors by reverse transcriptase–polymerase chain reaction and immunohistochemical analysis.



Results

Leptin was observed in SF obtained from human OA–affected joints, and leptin concentrations correlated with the body mass index. Marked expression of the protein was observed in OA cartilage and in osteophytes, while in normal cartilage, few chondrocytes produced leptin. Furthermore, the pattern and level of leptin expression were related to the grade of cartilage destruction and paralleled those of growth factors (IGF-1 and TGFβ1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes and induced the synthesis of IGF-1 and TGFβ1 in cartilage at both the messenger RNA and the protein levels.



Conclusion

These findings suggest a new peripheral function of leptin as a key regulator of chondrocyte metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.11303

Evidence for a key role of leptin in osteoarthritis.

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.

https://www.pnas.org/content/pnas/111/2/869.full.pdf

Suzanne N. Gardiner

Papers

Gender differences in serum leptin levels in humans.