Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK damage. Muscle mass is a key predictor of longevity in older adults, and obesity-induced sarcopenia is a significant risk factor for adverse health outcomes. Muscle is highly plastic, undergoes regular remodeling, and is responsible for the majority of total body glucose utilization, which when impaired leads to insulin resistance. Furthermore, impaired muscle integrity, defined as persistent muscle loss, intramuscular lipid accumulation, or connective tissue deposition, is a hallmark of metabolic dysfunction. In fact, many common inflammatory pathways have been implicated in the pathogenesis of the interrelated tissues of the musculoskeletal system (e.g., tendinopathy, osteoporosis, and osteoarthritis). Despite these similarities, these diseases are rarely evaluated in a comprehensive manner. The aim of this review is to summarize the common pathways that lead to musculoskeletal damage and disease that result from and contribute to MetS. We propose the overarching hypothesis that there is a central role for muscle damage with chronic exposure to an obesity-inducing diet. The inflammatory consequence of diet and muscle dysregulation can result in dysregulated tissue repair and an imbalance toward negative adaptation, resulting in regulatory failure and other musculoskeletal tissue damage. The commonalities support the conclusion that musculoskeletal pathology with MetS should be evaluated in a comprehensive and integrated manner to understand risk for other MSK-related conditions. Implications for conservative management strategies to regulate MetS are discussed, as are future research opportunities.

Summary. The purpose of this study is to relate student self‐concept in seven different areas to teacher ratings of student self‐concept in the same areas and to academic ability. The results from three diverse samples are considered (total N = 958 students). Student‐teacher agreement on student self‐concept varied from modest (r = 0.24 for Relationship With Parents) to good (r = 0.52 for Mathematics Self‐concept) for the seven self‐concept dimensions (mean r = 0.40), was higher in academic areas than non‐academic areas, and was particularly good for academic self‐concept in the high SES sample (r = 0.74). A multitrait‐multimethod analysis of this student‐teacher agreement demonstrated the distinctiveness of the seven dimensions and argued for the multidimensionality of self‐concept. Academic abilities (reading achievement, IQ, and teacher ratings of ability in different areas) tended to be uncorrelated with non‐academic dimensions of self‐concept, moderately correlated with the academic dimensions, and most highly correlated with the academic dimension of self‐concept that most closely matched the particular academic ability. These correlations were largest in the high SES sample where several correlations exceeded 0.7. Further discussion suggested possible reasons why the results of this study provide better support for the construct validity of self‐concept than is typically reported.

The Self-Description Questionnaire (SDQ) is a multidimensional instrument designed to measure seven facets of self-concept hypothesized in Shavelson's hierarchical model. The SDQ, along with measures of attributions and academic achievement, was administered to primary school students from two quite diverse populations. Separate factor analyses of responses from the two groups were similar and clearly demonstrated the seven factors that the SDQ is designed to measure. The small correlations among the different dimensions were similar for the two groups and consistent with the hierarchical structure in Shavelson's model. Consistent and predictable correlations were also observed between the different self-concept dimensions and (a) attributions of responsibility for academic outcomes, (b) academic achievement, and (c) the sex of the student. Smaller sex differences were observed for students who attended single-sex classes, suggesting that these students might be using a different reference group in forming their self-concepts. Overall, the findings provide compelling support for Shavelson's model, the construct validity of self-concept, and the validity of interpretations based upon the SDQ.

The influence of subthalamic nucleus (STN) afferents on dopaminergic (DA) neurons of the rat substantia nigra (SN) was investigated. Hemisections of the brain placed between the STN and the SN or located anterior to the STN caused an increase in the firing rate of DA cells without producing significant changes in their firing pattern. In contrast, electrolytic and ibotenic acid lesions of the STN resulted in 93% and 49% reductions, respectively, in the level of burst firing without affecting the firing rate of DA cells recorded in the lateral SN. Furthermore, procedures which interrupted the STN input to the SN produced rapid pacemaker-like firing in 18% of the lateral SN DA neurons recorded. Activation of the STN using single pulses of electrical stimulation caused: 1) a 20-50 msec inhibition of DA cell firing followed by an excitation, which in 35% of DA cells was accompanied by spikes occurring in a burst-like pattern, and 2) a short-latency inhibition lasting 5-25 msec in 75% of non-DA SN zona reticulata (ZR) neurons. On the other hand, stimulation of the STN for 1 minute at 20 Hz resulted in an initial decrease in DA cell burst firing followed by elevated firing rates and increased burst firing by 30-60 minutes after the stimulation. Pharmacological activation of the STN by infusion of bicuculline caused a rapid inhibition of DA cells followed by a two-fold increase in burst firing 6-14 minutes later, whereas SN ZR cells responded with an elevation in firing rate which dissipated in 6-14 minutes. Muscimol-induced STN inhibition produced complimentary biphasic changes in SN neuron firing: 1) an initial increase followed by a decrease in burst firing and firing rate of DA neurons and 2) a rapid inhibition followed by an excitation of ZR cells over a similar time course. Thus, the STN appears to exert a dual action on SN DA cells: 1) initial inhibition possibly mediated through STN excitation of the inhibitory SN ZR projections to DA cells, and 2) a facilitation of burst firing which may be a direct effect of excitatory STN afferents.

Sarcolipin (SLN) regulates muscle-based nonshivering thermogenesis and is up-regulated with high-fat feeding (HFF). To investigate whether other muscle-based thermogenic systems compensate for a lack of Sln and to firmly establish SLN as a mediator of diet-induced thermogenesis (DIT), we measured muscle and whole-body energy expenditure in chow- and high-fat-fed Sln(-/-) and wild-type (WT) mice. Following HFF, resting muscle metabolic rate (VO2, μl/g/s) was increased similarly in WT (0.28±0.02 vs. 0.31±0.03) and Sln(-/-) (0.23±0.03 vs. 0.35±0.02) mice due to increased sympathetic nervous system activation in Sln(-/-) mice; however, whole-body metabolic rate (VO2, ml/kg/h) was lower in Sln(-/-) compared with WT mice following HFF but only during periods when the mice were active in their cages (WT, 2894±87 vs. Sln(-/-), 2708±61). Treatment with the β-adrenergic receptor (β-AR) antagonist propranolol during HFF completely prevented muscle-based DIT in Sln(-/-) mice; however, it had no effect in WT mice, resulting in greater differences in whole-body metabolic rate and diet-induced weight gain. Our results suggest that β-AR signaling partially compensates for a lack of SLN to activate muscle-based DIT, but SLN is the primary and more effective mediator.