Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes

Considering the major role of insulin signaling on fatty acid synthesis via stimulation of lipogenic enzymes, differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis have been investigated by comparing the individual lipogenic fluxes in WT and IRS-1 knockout (IRS-1 KO) brown adipocytes. Results from experiments on WT and IRS-1 KO cells incubated with [5-¹³C] glutamine were consistent with the existence of reductive carboxylation pathway. Analysis of isotopomer distribution of nine metabolites related to the lipogenic routes from glucose and glutamine in IRS-1 KO cells using [U-¹³C] glutamine as compared to that in WT cells indicated that flux through reductive carboxylation pathway was diminished while flux through conventional TCA cycle was stimulated due to absence of insulin signaling in IRS-1 KO cells. This observation was confirmed by quantitative estimation of individual lipogenic fluxes in IRS-1 KO cells and their comparison with fluxes in WT cells. Thus, these results suggest that glutamine’s substantial contribution to fatty acid synthesis can be directly manipulated by controlling the flux through reductive carboxylation of alpha-ketoglutarate to citrate using hormone (insulin).

The Individual is Nothing, the Class Everything: Psychophysics and Modeling of Recognition in Obect Classes

Most psychophysical studies of object recognition have focussed on the recognition and representation of individual objects subjects had previously explicitely been trained on. Correspondingly, modeling studies have often employed a 'grandmother'-type representation where the objects to be recognized were represented by individual units. However, objects in the natural world are commonly members of a class containing a number of visually similar objects, such as faces, for which physiology studies have provided support for a representation based on a sparse population code, which permits generalization from the learned exemplars to novel objects of that class. In this paper, we present results from psychophysical and modeling studies intended to investigate object recognition in natural ('continuous') object classes. In two experiments, subjects were trained to perform subordinate level discrimination in a continuous object class - images of computer-rendered cars - created using a 3D morphing system. By comparing the recognition performance of trained and untrained subjects we could estimate the effects of viewpoint-specific training and infer properties of the object class-specific representation learned as a result of training. We then compared the experimental findings to simulations, building on our recently presented HMAX model of object recognition in cortex, to investigate the computational properties of a population-based object class representation as outlined above. We find experimental evidence, supported by modeling results, that training builds a viewpoint- and class-specific representation that supplements a pre-existing repre-sentation with lower shape discriminability but possibly greater viewpoint invariance.