Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet

Hypertension and elevated sympathetic drive result from consumption of a high-calorie diet and deposition of abdominal fat, but the etiology and temporal characteristics are unknown. Rabbits instrumented for telemetric recording of arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat diet for 3 weeks then control diet for 1 week or control diet for 4 weeks. Baroreflexes and responses to air-jet stress and hypoxia were determined weekly. After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, heart rate and RSNA did not change further. The RSNA baroreflex was attenuated from the first week of the diet. Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a normal diet returned glucose, insulin, leptin, and heart rate to control levels, but body weight, mean arterial pressure, and RSNA remained elevated. In conclusion, elevated sympathetic drive and impaired baroreflex function, which occur within 1 week of consumption of a high-fat, high-calorie diet, appear integral to the rapid development of obesity-related hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of mean arterial pressure, which likely lies in alterations in the response of neurons in the hypothalamus.

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

Objective:

The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease.
Subjects:

We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass.
Results:

Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10−5). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele.
Conclusions:

Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.

Reduced preprandial dipping accounts for rapid elevation of blood pressure and renal sympathetic nerve activity in rabbits fed a high-fat diet

Consumption of a high-fat diet (HFD) by rabbits results in increased blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) within 1 wk. Here, we determined how early this activation occurred and whether it was related to changes in cardiovascular and neural 24-h rhythms. Rabbits were meal-fed a HFD for 3 wks, then a normal-fat diet (NFD) for 1 wk. BP, HR, and RSNA were measured daily in the home cage via implanted telemeters. Baseline BP, HR, and RSNA over 24 h were 71 ± 1 mm Hg, 205 ± 4 beats/min and 7 ± 1 normalized units (nu). The 24-h pattern was entrained to the feeding cycle and values increased from preprandial minimum to postprandial maximum by 4 ± 1 mm Hg, 51 ± 6 beats/min, and 1.6 ± .6 nu each day. Feeding of a HFD markedly diminished the preprandial dip after 2 d (79–125% of control; p < 0.05) and this reduction lasted for 3 wks of HFD. Twenty-four-hour BP, HR, and RSNA concurrently increased by 2%, 18%, and 22%, respectively. Loss of preprandial dipping accounted for all of the BP increase and 50% of the RSNA increase over 3 wks and the 24-h rhythm became entrained to the light-dark cycle. Resumption of a NFD did not alter the BP preprandial dip. Thus, elevated BP induced by a HFD and mediated by increased sympathetic nerve activity results from a reduction in preprandial dipping, from the first day. Increased calories, glucose, insulin, and leptin may account for early changes, whereas long-term loss of dipping may be related to increased sensitivity of sympathetic pathways.

Musculoskeletal deterioration in men accompanies increases in body fat

Objective
To examine body fat and musculoskeletal changes in men over 5 years.

Methods
Body composition was evaluated for men in the Geelong Osteoporosis Study using whole body dual energy X-ray absorptiometry (DXA) during two time-periods. DXA was performed for 1329 men (25-96 years) during 2001-2006 and for 900 men (25-98 years), 2006-2011. The masses of fat, lean, and bone were expressed relative to the square of height (kg/m2). Each compartment was also expressed as a percentage relative to body weight (%fat, %lean, %bone).

Results
Mean BMI increased from 26.9 kg/m2 in 2001-2006, to 27.2 kg/m2 in 2006-2011 (P = 0.04). Mean fat mass increased by 9.0% from 6.98 kg/m2 (95%CI 6.84-7.11) in 2001-2006, to 7.60 kg/m2 (7.44-7.77) in 2006-2011 (P < 0.001); mean lean mass decreased by 0.9%, from 18.92 kg/m2 (18.83-19.01) to 18.75 kg/m2 (18.64-18.86) (P = 0.02), and mean bone mass decreased 1.6% from 1.041 kg/m2 (1.034-1.047), to 1.024 kg/m2 (1.016-1.032). Mean %fat increased from 23.4% to 25.2%, mean %lean decreased from 72.6% to 70.9% and mean %bone decreased from 4.0% to 3.9% (all P < 0.05).

Conclusions
An increase in BMI, which reflects a substantial increase in body fat mass and declines in both lean and bone mass was reported. This may have implications for future development of bone fragility, sarcopenia, and sarcopenic obesity.