Noga Kronfeld-Schor

SIRT6 protects against pathological damage caused by diet-induced obesity

The NAD+‐dependent SIRT6 deacetylase is a therapeutic candidate against the emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in premature aging phenotypes and metabolic defects, was implicated in a calorie restriction response that showed an opposite set of phenotypes from the metabolic syndrome. To explore the role of SIRT6 in metabolic stress, wild type and transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison to their wild‐type littermates, SIRT6 TG mice accumulated significantly less visceral fat, LDL‐cholesterol, and triglycerides. TG mice displayed enhanced glucose tolerance along with increased glucose‐stimulated insulin secretion. Gene expression analysis of adipose tissue revealed that the positive effect of SIRT6 overexpression is associated with down regulation of a selective set of peroxisome proliferator‐activated receptor‐responsive genes, and genes associated with lipid storage, such as angiopoietin‐like protein 4, adipocyte fatty acid‐binding protein, and diacylglycerol acyltransferase 1, which were suggested as potential targets for drugs to control metabolic syndrome. These results demonstrate a protective role for SIRT6 against the metabolic consequences of diet‐induced obesity and suggest a potentially beneficial effect of SIRT6 activation on age‐related metabolic diseases.

Seasonal Thermogenic Acclimation of Diurnally and Nocturnally Active Desert Spiny Mice

Diurnally active golden spiny mice (Acomys russatus) and nocturnal common spiny mice (Acomys cahirinus) coexist in hot rocky deserts of Israel. Diurnal and nocturnal activities expose these species to different climatic conditions. Nonshivering thermogenesis (NST) capacity of individuals of both species immediately upon removal from the field exhibited seasonal changes, with no significant interspecific difference. Colony‐reared mice of either species transferred in the laboratory from long to short photoperiod increased NST capacity, though to a lesser extent than observed in the seasonal acclimatization. The underlying biochemical mechanisms of short photoperiod acclimation differed between the species. In both Cytochrome‐c oxidase (Cox) activity was higher in short as compared to long photoperiod. In short‐photoperiod‐acclimated A. cahirinus uncoupling protein (UCP) content in brown adipose tissue (BAT) was significantly higher than in long photoperiod, while in A. russatus there was no significant change. In A. russatus there was a significant increase in lipoprotein lipase (LPL) activity in BAT in short‐photoperiod‐acclimated individuals, while in A. cahirinus LPL activity was high under both acclimations. The low LPL activity in brown adipose tissue of desert‐adapted A. russatus may facilitate lipid uptake in white adipose tissue, an advantage in desert conditions where food is scarce and irregularly distributed in space and time.

The dietary basis for temporal partitioning: food habits of coexisting Acomys species

Abstract Two rodent species of the genus Acomys coexist on rocky terrain in the southern deserts of Israel. The common spiny mouse (A. cahirinus) is nocturnally active whereas the golden spiny mouse (A. russatus) is diurnally active. An early removal study suggested that competition accounts for this pattern of temporal partitioning: the golden spiny mouse is forced into diurnal activity by its congener. Theoretically, temporal segregation should facilitate coexistence if the shared limiting resources differ at different times (primarily among predators whose prey populations have activity rhythms), or if they are renewed within the period of the temporal segregation. We studied food preferences of the two Acomys species in a controlled cafeteria experiment in order to assess resource overlap and the potential for competition for food between the two species. We found no significant difference in food preferences between species. The dietary items preferred by both were arthropods. We also carried out a seasonal study of the percentage and identity of arthropods taken in the field by individuals of the two species. Individuals of both species took on annual average a high percentage of arthropods in their diets. Seasonal diet shifts reflect seasonal abundance of arthropods at Ein Gedi during day and night. Diurnal activity may also reduce interspecific interference competition between A. russatus and A. cahirinus. However, the strong interspecific dietary overlap in food preference, the heavy reliance on arthropods in spiny mouse diets, and the seasonal and circadian differences in arthropod consumption suggest that prey partitioning may be a viable mechanism of coexistence in this system.

On the role of phylogeny in determining activity patterns of rodents

Evolutionary plasticity is limited, to a certain extent, by phylogenetic constraints. We asked whether the diel activity patterns of animals reflect their phylogenies by analyzing daily activity patterns in the order Rodentia. We carried out a literature survey of activity patterns of 700 species, placing each in an activity time category: diurnal, nocturnal, or active at both periods (a-rhythmic). The proportion of rodents active at these categories in the entire order, was compared to the activity patterns of species of different families for which we had data for over ten species each: Dipodidae, Echimyidae, Geomyidae, Heteromyidae, Muridae, and Sciuridae. Activity times of rodents from different habitat types were also compared to the ordinal activity time pattern. We also calculated the probability that two random species (from a particular subgroup: family, habitat, etc.) will be active in the same period of the day and compared it to this probability with species drawn from the entire order. Activity patterns at the family level were significantly different from the ordinal pattern, emphasizing the strong relationship between intra-family taxonomic affiliation and daily activity patterns. Large families (Muridae and Sciuridae) analyzed by subfamilies and tribes showed a similar but stronger pattern than that of the family level. Thus it is clear that phylogeny constrains the evolution of activity patterns in rodents, and may limit their ability to use the time niche axis for ecological separation. Rodents living in cold habitats differed significantly from the ordinal pattern, showing more diurnal and a-rhythmic activity patterns, possibly due to physiological constraints. Ground-dwelling rodents differed significantly, showing a high tendency towards a-rhythmic activity, perhaps reflecting their specialized habitat.

Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent.

The present study examined the effect of simulated change in day length on the behavior of a diurnal rodent, the fat sand rat (a species of gerbil). Animals were housed under a short photoperiod (5/19 light/dark cycle) for 3 weeks and compared with controls living under a 12/12 light/dark cycle. All sand rats then underwent the forced swim test for depression-like behavior, and the open-field test for overall activity. Sand rats exposed to the short photoperiod displayed a significantly earlier sinking in the swim test, but there was no difference between their open-field activity compared with controls. Taking these responses as indicative of depression-like behavior, we suggest that a short photoperiod may induce affective-like changes, and that the sand rat may thus offer an appropriate animal model to explore the effect of photoperiod on normal, and perhaps also abnormal, seasonal mood changes (e.g., SAD), which in humans is a prevalent disorder, with winter depression episodes and spring/summer remissions.

On the Use of the Time Axis for Ecological Separation: Diel Rhythms as an Evolutionary Constraint

Temporal partitioning as a mechanism of coexistence among competitors has seldom been explored and is considered uncommon (Schoener 1986). Understanding ecological and evolutionary plasticity in use of the temporal niche axis is significant for assessing the potential for temporal partitioning and may be key to understanding the relative rarity of this phenomenon. Daily rhythms in mammalian physiology, hormone concentrations, biochemistry, and behavior are driven by an internal circadian clock that is entrained to the predictable 24-h change in light intensity (Heldmaier et al. 1989; Refinetti et al. 1992; Smith et al. 1998). Entrainment to this overriding cue (“zeitgeber”) allows mammals to choose the right time for a given response or activity without being easily misled by minor environmental disturbances (Aronson et al. 1993). Thus, a degree of rigidity to environmental nonphotic stimuli is built into the circadian system. However, under laboratory conditions, small mammals can be forced to shift their locomotor activity patterns by nonphotic stimuli (Mistlberger 1991; Cambras et al. 1993; Challet et al. 1997; Brinkhof et al. 1998), indicating that activity is not tightly controlled by the circadian clock

Chronobiology by moonlight

Most studies in chronobiology focus on solar cycles (daily and annual). Moonlight and the lunar cycle received considerably less attention by chronobiologists. An exception are rhythms in intertidal species. Terrestrial ecologists long ago acknowledged the effects of moonlight on predation success, and consequently on predation risk, foraging behaviour and habitat use, while marine biologists have focused more on the behaviour and mainly on reproduction synchronization with relation to the Moon phase. Lately, several studies in different animal taxa addressed the role of moonlight in determining activity and studied the underlying mechanisms. In this paper, we review the ecological and behavioural evidence showing the effect of moonlight on activity, discuss the adaptive value of these changes, and describe possible mechanisms underlying this effect. We will also refer to other sources of night-time light (‘light pollution’) and highlight open questions that demand further studies.

We are in the dark here: induction of depression- and anxiety-like behaviours in the diurnal fat sand rat, by short daylight or melatonin injections.

Circadian rhythms are considered an important factor in the aetiology, expression and treatment of major affective disorders, including seasonal affective disorder (SAD). However, data on the effects of daylight length manipulation or melatonin administration are complex. It has been suggested that since diurnal and nocturnal mammals differ significantly in their physiological and behavioural responses to daylight, diurnal rodents offer a preferable model of disorders related to circadian rhythms in the diurnal human. We previously found that diurnal fat sand rats maintained under short daylight (SD), show depression-like behaviour in the forced swim test (FST). The present study was designed to test additional behaviours related to affective disorders and study the involvement of melatonin in these behaviours. Sand rats were divided into short-daylight (SD, 5 h light:19 h dark) and long-daylight (LD, 12 h light:12 h dark) groups, and received 100 microg melatonin or vehicle administration for 3 wk (5 h and 8.5 h after light onset in the LD room). Animals were then tested for reward-seeking behaviour (saccharin consumption), anxiety (elevated plus-maze), aggression (resident-intruder test), and depression-like behaviour (FST). SD or melatonin administration resulted in a depressed/anxious-like behavioural phenotype including reduced reward seeking, increased anxiety, decreased aggression and decreased activity in the FST, supporting the notion that in a diurnal animal, reduced light results in a variety of behavioural changes that may model depression and anxiety; and that melatonin may be a significant factor in these changes. We suggest that the sand rat may offer an excellent model species to explore the interactions between daylight, affective behaviour and the related underlying mechanisms.

Activity patterns of rodents: the physiological ecology of biological rhythms

To date, most research in the field of biological rhythms has been performed on nocturnal rodents under laboratory conditions. This research has made much progress in recent years. It is now time to investigate the adaptive value of the studied molecular mechanisms under natural conditions. Here we review relevant studies of rodent activity patterns. We also review a case study of temporal partitioning between spiny mice. We conclude that the response to environmental stimuli, using a system composed of a rigid master circadian oscillator and more flexible mechanisms such as peripheral oscillators with weak coupling, masking responses, and downstream switching mechanisms, is adaptive since it enables an animal to reset its activity phase without the cost of shifting the phase of the entire circadian system. We suggest that these mechanisms play a significant role in determining activity patterns under natural conditions, and are important for understanding the ecology and evolution of activity rhythms.

POPULATION BIOLOGY AND SPATIAL RELATIONSHIPS OF COEXISTING SPINY MICE (ACOMYS) IN ISRAEL

Abstract Nocturnally active Acomys cahirinus and diurnally active A. russatus cooccur in hot rocky deserts, and their temporal partitioning results from competition. We studied their population biology at Ein Gedi near the Dead Sea to determine their spatial relationships and gain insight into their ecological overlap. Individuals of both species were trapped repeatedly for almost 2 years. Mean body mass did not change seasonally, and A. russatus was significantly heavier than A. cahirinus. Density of A. russatus was significantly greater than that of A. cahirinus. Acomys russatus had a shorter reproductive peak that overlapped the longer reproductive season of A. cahirinus. Acomys russatus showed a significant preference for boulder habitat versus open habitat at all seasons, whereas A. cahirinus showed a preference for boulder habitat only half of the time. Sexes of both species overlapped in home range.