Upright walking absent a bent-hip-bent-knee gait requires lumbar lordosis, a ubiquitous feature in all hominids for which it can be observed. Its first appearance is therefore a central problem in human evolution. Atelids, which use the tail during suspension, exhibit demonstrable lordosis and can achieve full extension of their hind limbs during terrestrial upright stance. Although obviously homoplastic with hominids, the pelvic mechanisms facilitating lordosis appear largely similar in both taxa with respect to abbreviation of upper iliac height coupled with broad sacral alae. Both provide spatial separation of the most caudal lumbar(s) from the iliac blades. A broad sacrum is therefore a likely facet of earliest hominid bipedality. All tailed monkeys have broad alae. By contrast all extant apes have very narrow sacra, which promote “trapping” of their most caudal lumbars to achieve lower trunk rigidity during suspension. The alae in the tailless proconsul Ekembo nyanzae appear to have been quite broad, a character state that may have been primitive in Miocene hominoids not yet adapted to suspension and, by extension, exaptive for earliest bipedality in the hominid/panid last common ancestor. This hypothesis receives strong support from other anatomical systems preserved in Ardipithecus ramidus.
The sacral/caudal boundary appears to be displaced cranially in early hominids relative to extant African apes and humans, a condition consistent with the likely ancestral condition for Miocene hominoids. While not definitive in itself, a four-segmented sacrum accords well with the "long-back" model for the Pan/Homo last common ancestor. Am J Phys Anthropol 160:729-739, 2016. © 2016 Wiley Periodicals, Inc.
Childhood obesity is increasing at an alarming rate. Tall stature and accelerated skeletal maturation are hallmarks of obesity that have detrimental consequences such as limb bowing, slipped epiphyses, and fractures, which rapidly evolve into adult disability. One major treatment obstacle is lack of knowledge of the underlying cause of this growth acceleration. Circulating IGF‐1, the major hormone required for growth, is paradoxically low to normal in obese children. Obesity is characterized by chronic inflammation driven by cytokines such as interleukin‐6 (IL‐6), which suppresses bone elongation by inhibiting IGF‐1. Our lab found that a high‐fat diet accelerates bone elongation in mice before they had excess body fat, indicating that skeletal impacts of a high‐fat diet are well underway before physical signs of obesity emerge. Our goal was to determine whether high‐fat diet alters inflammatory cytokines that could serve as biomarkers for skeletal damage. We tested the HYPOTHESIS that mice on a high‐fat diet have higher levels of inflammatory cytokines before they exhibit overt obesity. METHODS Female and male 3‐week‐old C57BL/6 mice (N=6/diet/age) were put on high‐fat (60% kCal fat) or control (10% kCal fat) diets for 1 or 2 weeks. Serum cytokines (Leptin, TNF‐α, IGF‐1, IL‐6, VEGF, IL‐1α, IL‐1β, MCP‐1) were measured by ELISA, and glucose was measured with a blood glucose monitor. Statistical significance (p<0.05) was determined in SPSS using Mann‐Whitney and t‐tests. RESULTS At 4 weeks, after 1 week on diet, tibial elongation rate was over 20% higher in mice on a high‐fat diet (t=4.4, p<0.001) and body mass was 16% greater (t=5.6, p<0.001), though mice were not yet obese. By 5‐weeks, after 2 weeks on diet, tibial elongation rate was still over 10% higher in the high‐fat diet group (t=2.1, p<0.05) but with no difference in body mass (t=0.5, p=0.62). At 4‐weeks, IGF‐1 (z=2.3, p<0.05), IL‐6 (z=2.4, p<0.05), and IL‐1α (z=2.3, p<0.05) were all significantly decreased in the high‐fat diet mice. At 5‐weeks, TNF‐α (z=2.9, p<0.01) and IL‐6 (z=2.7, p<0.01) were decreased in the high‐fat diet group, while VEGF (z=2.7, p<0.01) was increased. There were no differences in glucose between diets at either age. DISCUSSION Our results support the hypothesis that a high‐fat diet alters inflammatory cytokines before the overt onset of obesity. Unexpectedly, most cytokines were decreased rather than increased as predicted. The most robust finding was the 2‐fold and 1.5‐fold decrease in IL‐6 at the 4‐ and 5‐week age points, respectively. In addition to inflammation, IL‐6 can regulate energy metabolism, with low IL‐6 possibly contributing to human obesity. Decreased IL‐6 is also consistent with our finding of increased bone elongation since high IL‐6 suppresses growth. SIGNIFICANCE These results are relevant for understanding the development of obesity‐related skeletal complications. Reduced inflammatory cytokines, particularly IL‐6, during juvenile growth could be a useful biomarker for assessing potential skeletal damage before a ch...
Nearly one-third of children in the United States are overweight or obese by their pre-teens. Tall stature and accelerated bone elongation are characteristic features of childhood obesity, which co-occur with conditions such as limb bowing, slipped epiphyses, and fractures. Obese children paradoxically have normal circulating IGF-I, the major growth-stimulating hormone. Here we describe and validate a mouse model of excess dietary fat to examine mechanisms of growth acceleration in obesity. We used in vivo multiphoton imaging and immunostaining to test the hypothesis that high-fat diet increases IGF-I activity and alters growth plate structure before the onset of obesity. We tracked bone and body growth in male and female C57BL/6 mice (N = 114) on high-fat (60% kcal fat) or control (10% kcal fat) diets from weaning (3-weeks) to skeletal maturity (12-weeks). Tibial and tail elongation rates increased after brief (1-2 week) high-fat diet exposure without altering serum IGF-I. Femoral bone density and growth plate size were increased, but growth plates were disorganized in not-yet-obese high-fat diet mice. Multiphoton imaging revealed more IGF-I in the vasculature surrounding growth plates of high-fat diet mice, and increased uptake when vascular levels peaked. High-fat diet growth plates had more activated IGF-I receptors and fewer inhibitory binding proteins, suggesting increased IGF-I bioavailability in growth plates. These results, which parallel pediatric growth patterns, highlight the fundamental role of diet in the earliest stages of developing obesity-related skeletal complications and validate the utility of the model for future studies aimed at determining mechanisms of diet-enhanced bone lengthening.
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