The gravitostat protects diet‐induced obese rats against fat accumulation and weight gain

Abstract

The gravitostat is a novel homeostatic body weight‐regulating mechanism, mostly studied in mice, and recently confirmed in obese humans. In the present study, we explored the effect of weight loading on metabolic outcomes, meal patterns and parameters linked to energy expenditure in both obese and lean rats. Diet‐induced obese (DIO) and lean rats were implanted with capsules weighing either 15% of biological body weight (load) or empty capsules (1.3% of body weight; controls). Loading protected against fat accumulation more markedly in the DIO group. In line with this, the obesity‐related impairment in insulin sensitivity was notably ameliorated in DIO rats upon loading, as revealed by the reduction in serum insulin levels and homeostatic model assessment for insulin resistance index scores. Although 24‐hour caloric intake was reduced in both groups, this effect was greater in loaded DIO rats than in loaded lean peers. During days 10‐16, after recovery from surgery, loading: (i) decreased meal size in both groups (only during the light phase in DIO rats) but this was compensated in lean rats by an increase in meal frequency; (ii) reduced dark phase locomotor activity only in lean rats; and (iii) reduced mean caloric efficiency in DIO rats. Muscle weight was unaffected by loading in either group. Dietary‐obese rats are therefore more responsive than lean rats to loading.

Highly recruited brown adipose tissue does not in itself protect against obesity

“…Functionally, this is ascribed to the brain being informed of the status of the body's energy reserves and thus taking adequate countermeasures if body weight/body energy reserves deviate from desired levels [ [41] , [42] , [43] , [44] , [45] ]. Leptin is generally thought to be the (main) conveyer of this information from the periphery to the brain [ 46 ], but there are indications that other systems may be involved [ [47] , [48] , [49] , [50] ]. The general question as to whether such a system for body weight control really exists, with a set point or with settling points, and how it could develop, has been discussed, based on e.g.…”

The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions

“…Importantly, we have demonstrated that the homeostatic body mass reducing effect of increased loading by weight capsules is much more efficient in obese mice on high fat diet than in lean mice on normal chow diet [17,28,29]. This key finding explains the previously observed less pronounced effects of increased loading using rodents on normal chow diet as seen by others and initially also by us [17,[25][26][27][28][29]. The use of obese mice on high fat diet, mimicking human obesity, enabled us, in several articles, to demonstrate that the loading effect is observed for both male and female mice and for both intraperitoneal and subcutaneous implantation of weight capsules [17,28,29].…”

“…In addition, approximately 20 years ago, two independent research groups demonstrated that intraperitoneal implantation of inert weight capsules partly reduced (by ca 50% of the added weight) the biological body weight in proportion to the added weights in male but not female rodents on normal chow diet [ 25 – 27 ]. Importantly, we have demonstrated that the homeostatic body mass reducing effect of increased loading by weight capsules is much more efficient in obese mice on high fat diet than in lean mice on normal chow diet [ 17 , 28 , 29 ]. This key finding explains the previously observed less pronounced effects of increased loading using rodents on normal chow diet as seen by others and initially also by us [ 17 , 25 – 29 ].…”

“…This key finding explains the previously observed less pronounced effects of increased loading using rodents on normal chow diet as seen by others and initially also by us [ 17 , 25 – 29 ]. The use of obese mice on high fat diet, mimicking human obesity, enabled us, in several articles, to demonstrate that the loading effect is observed for both male and female mice and for both intraperitoneal and subcutaneous implantation of weight capsules [ 17 , 28 , 29 ]. Thus, data from three independent laboratories using implantation of weight capsules and multiple independent studies using centrifugation support the notion that increased loading reduces body mass in rodents.…”

The fructose survival hypothesis for obesity

“…hyperphagia, leptin resistance, weight gain and fat accumulation, fatty liver and insulin resistance) but shortly before they hibernate they reduce their food intake even though food may still be available and this is associated with a decrease in their metabolism [ 135 , 136 ]. One likely mechanism may relate to reaching a weight that triggers biologic response to reduce food intake (the gravitostat) [ 137 , 138 ]. While this mechanism still occurs in obese humans [ 139 ], it is apparent that it can be overrun, which we speculate may relate to continued exposure to high concentrations of fructose.…”