Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

Background

Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.

Methods

Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.

Results

Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.

Conclusion

Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy deficit in mice.     

The DTH-initiating Thy-1+ cell is double-negative (CD4-, CD8-) and CD3-, and expresses IL-3 receptors, but no IL-2 receptors

The elicitation of delayed-type hypersensitivity (DTH) requires an early-acting Thy-1+ cell that produces an Ag-specific, non-MHC-restricted factor that initiates DTH by sensitizing the local tissue for release of the vasoactive amine serotonin. We characterized the phenotype of this DTH-initiating cell by treating cells from sensitized mice with different antibodies and then either with rabbit C or anti-Ig panning or bead separation to deplete various subpopulations. We then transferred these cells i.v. into naive recipients that were challenged to elicit DTH. Our findings indicate that the early DTH-initiating cell is Thy-1+, Lyt-1+, CD4-, CD8- and CD3-, whereas the classical, late DTH effector T cell is Thy-1+, Lyt-1+, CD4+, CD8-, and CD3+. We hypothesize that DTH-initiating cells are primitive T cells with Ag receptors that can bind Ag without MHC-restriction. This hypothesis was supported by the finding that two different antibodies, that both bind T cell-derived Ag-binding molecules, eliminated the DTH-initiating, cell but did not affect the late component, MHC-restricted CD4+, CD3+ T cell. Additional experiments with antibodies against restricted determinants of the T-200 glycoprotein family (CD45R) showed that the early but not the late cell is positive for B220, which is usually present on B cells, and on some activated T cells. Also, the DTH-initiating cell is Il-2R-, but Il-3R+; whereas the late component DTH T cell is IL-2R+ and IL-3-. Our findings suggest that DTH-initiating cells may be Ag-specific lymphoid precursor cells that arise before final differentiation along the pathway leading to mature T or B cells. Our results indicate that antigen-specific Thy-1+, CD3-, CD4-, CD8- cells function in vivo to initiate DTH reactions.     

The role of viscoelasticity of collagen fibers in articular cartilage: theory and numerical formulation

The relative importance of fluid-dependent and fluid-independent transient mechanical behavior in articular cartilage was examined for tensile and unconfined compression testing using a fibril reinforced model. The collagen matrix of articular cartilage was modeled as viscoelastic using a quasi-linear viscoelastic formulation with strain-dependent elastic modulus, while the proteoglycan matrix was considered as linearly elastic. The collagen viscoelastic properties were obtained by fitting experimental data from a tensile test. These properties were used to investigate unconfined compression testing, and the sensitivity of the properties was also explored. It was predicted that the stress relaxation observed in tensile tests was not caused by fluid pressurization at the macroscopic level. A multi-step tensile stress relaxation test could be approximated using a hereditary integral in which the elastic fibrillar modulus was taken to be a linear function of the fibrillar strain. Applying the same formulation to the radial fibers in unconfined compression, stress relaxation could not be simulated if fluid pressurization were absent. Collagen viscoelasticity was found to slightly weaken fluid pressurization in unconfined compression, and this effect was relatively more significant at moderate strain rates. Therefore, collagen viscoelasticity appears to play an import role in articular cartilage in tensile testing, while fluid pressurization dominates the transient mechanical behavior in compression. Collagen viscoelasticity plays a minor role in the mechanical response of cartilage in unconfined compression if significant fluid flow is present.     

Force-length properties and functional demands of cat gastrocnemius, soleus and plantaris muscles.

The purpose of this study was to measure isometric force-length properties of cat soleus, gastrocnemius and plantaris muscle-tendon units, and to relate these properties to the functional demands of these muscles during everyday locomotor activities. Isometric force-length properties were determined using an in situ preparation, where forces were measured using buckle-type tendon transducers, and muscle-tendon unit lengths were quantified through ankle and knee joint configurations. Functional demands of the muscles were assessed using direct muscle force measurements in freely moving animals. Force-length properties and functional demands were determined for soleus, gastrocnemius and plantaris muscles simultaneously in each animal. The results suggest that isometric force-length properties of cat soleus, gastrocnemius and plantaris muscles, as well as the region of the force-length relation that is used during everyday locomotor tasks, match the functional demands.     

Sensitivity of muscle force estimations to changes in muscle input parameters using nonlinear optimization approaches.

The purpose of this study was to analyze the sensitivity of muscle force calculations to changes in muscle input parameters. Force sharing between two synergistic muscles was derived analytically for a one-degree-of-freedom system using three nonlinear optimization approaches. Changes in input parameters that are within normal anatomical variations often caused changes in muscular forces exceeding 100 percent. These results indicate that errors in muscle force calculations may depend as much on inadequate muscle input parameters as they may on the choice of the objective and constraint functions of the optimization approach.